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Few studies have examined the impact of late-life depression trajectories on specific domains of cognitive function. This study aims to delineate how different depressive symptom trajectories specifically affect cognitive function in older adults.
Design:
Prospective longitudinal cohort study
Setting:
Australia and the United States of America
Participants:
In total, 11,035 community-dwelling older adults with a mean age of 75 years
Measurements:
Depressive trajectories were modelled from depressive symptoms according to annual Centre for Epidemiological Studies Depression Scale 10 (CES-D-10) surveys. Four trajectories of depressive symptoms were identified: low (“nondepressed”), consistently mild (“subthreshold depression”), consistently moderate (“persistent depression”), and initially low but increasing (“emerging depression”). Global cognition (Modified Mini-Mental State Examination [3MS]), verbal fluency (Controlled Oral Word Association Test [COWAT]), processing speed (Symbol Digit Modalities Test [SDMT]), episodic memory (Hopkins Verbal Learning Test – Revised [HVLT-R]), and a composite z-score were assessed over a subsequent median 2 years.
Results:
Subthreshold depression predicted impaired performance on the SDMT (Cohen’s d −0.04) and composite score (−0.03); emerging depression predicted impaired performance on the SDMT (−0.13), HVLT-R (−0.09), 3 MS (−0.08) and composite score (−0.09); and persistent depression predicted impaired performance on the SDMT (−0.08), 3 MS (−0.11), and composite score (−0.09).
Conclusions:
Depressive symptoms are associated with later impaired processing speed. These effects are small. Diverse depression trajectories have different impacts on cognitive function.
An area of great interest in Depression and Mood Disorder research has been highlighted by the Mental Health Priority Area of the Wellcome Trust (UK), namely sleep and circadian rhythm disturbances (SCRD). Wellcome has set out the background logic for this focus and clear research priorities (Wellcome Trust, 2022), leading to the funding of a series of international projects. This focus is a particularly good fit with the international agenda for development of more effective and scalable strategies for prevention, early intervention and secondary prevention of illness relapse, progression and downstream physical illnesses for adolescent-onset anxiety, depressive and psychotic disorders (Hickie et al., 2019).
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Individuals living with severe mental illness can have significant emotional, physical and social challenges. Collaborative care combines clinical and organisational components.
Aims
We tested whether a primary care-based collaborative care model (PARTNERS) would improve quality of life for people with diagnoses of schizophrenia, bipolar disorder or other psychoses, compared with usual care.
Method
We conducted a general practice-based, cluster randomised controlled superiority trial. Practices were recruited from four English regions and allocated (1:1) to intervention or control. Individuals receiving limited input in secondary care or who were under primary care only were eligible. The 12-month PARTNERS intervention incorporated person-centred coaching support and liaison work. The primary outcome was quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA).
Results
We allocated 39 general practices, with 198 participants, to the PARTNERS intervention (20 practices, 116 participants) or control (19 practices, 82 participants). Primary outcome data were available for 99 (85.3%) intervention and 71 (86.6%) control participants. Mean change in overall MANSA score did not differ between the groups (intervention: 0.25, s.d. 0.73; control: 0.21, s.d. 0.86; estimated fully adjusted between-group difference 0.03, 95% CI −0.25 to 0.31; P = 0.819). Acute mental health episodes (safety outcome) included three crises in the intervention group and four in the control group.
Conclusions
There was no evidence of a difference in quality of life, as measured with the MANSA, between those receiving the PARTNERS intervention and usual care. Shifting care to primary care was not associated with increased adverse outcomes.
The research described in this Research Communication addresses the hypothesis that intramammary infections with Streptococcus uberis (S. uberis) are associated with biofilm formation, which limits antibiotic efficacy. This retrospective study investigated biofilm expression and antimicrobial resistance (AMR) patterns of 172 S. uberis infections. Isolates were recovered from milk samples of subclinical, clinical, and intramammary infection cases on 30 commercial dairy herds. We determined the presence and intensity of biofilm expression of S. uberis isolates in vitro in three somatic cell count categories to recognise their AMR patterns. An automated minimum inhibitory concentration system with a commercially available panel of 23 antimicrobial agents evaluated AMR, while biofilm determination was conducted using a microplate method. The study established that all the S. uberis isolates assessed expressed biofilm with the following varying degrees of intensities: 30 (17.8%) strong, 59 (34.9%) medium and 80 (47.3%) weak biofilms. The newly registered UBAC mastitis vaccine containing biofilm adhesion components may, therefore, be a viable option for proactive mastitis management under field conditions. No differences were identified between biofilm intensity and the three somatic cell count groups. Most S. uberis isolates indicated a high-level sensitivity to the antimicrobial agents tested. Resistances were present in 8.7, 8.1 and 7.0% cases to rifampin, minocycline and tetracycline, respectively. Multidrug resistance was observed in 6.4%, emphasising AMR to antibiotics used in human medicine only. The low overall resistance suggests that farmers adhere to the prudent use of antimicrobials in the dairy industry.
Receiving bad news about one’s health can be devastating, yet little is known about how the therapeutic nature of the environment where bad news is delivered affects the experience. The current study aimed to explore how patients and their families were affected by the language and the built, natural, social, and symbolic environments when receiving bad news, through the Therapeutic Landscapes theoretical framework.
Methods
Patients diagnosed with a life-limiting illness living in regional Victoria who had a hospital admission within 24 months and a diagnostic/prognostic conversation were invited to participate, as well as a family member who witnessed the conversation. Participants were recruited through social media and snowballing, resulting in 14 online semi-structured interviews being conducted between November 2021 and March 2022, audio-recorded, and transcribed verbatim. Reflexive thematic analysis was used to develop the themes.
Results
Fourteen semi-structured interviews were conducted with women aged between 30 and 77 years. Interviews lasted between 45 and 120 minutes, with an average of 69 minutes, and were conducted online or via mobile phone. Four central themes were developed: “Hearing bad news for the first time,” “Preferences for having hard conversations,” “Creating a sense of safety for ongoing care,” and “The therapeutic nature of the ward.”
Significance of results
This body of work will help inform practice and future policy regarding bad news delivery and the design and aesthetics of environments where bad news is delivered. It is essential that bad news is delivered within a quiet, calm, and emotionally safe environment within a supportive therapeutic relationship.
Understanding patient preferences and the demand for healthcare interventions and technology is critical for health technology assessment (HTA). New health technologies have potential for savings and increased efficiency but even the most cost-effective and efficacious interventions can fail if patient preferences are not properly accounted for. Patient preferences in HTA are primarily limited to representation in appraisal committees; however, more robust methods are available and should be incorporated into the assessment of interventions.
Methods
Using data from three discrete choice experiments (DCEs), we reflect on the importance of patient preferences in the design of healthcare interventions. We draw insights from three studies which investigated preferences relating to HIV self-testing amongst long distance truck drivers in Kenya; differentiated antiretroviral therapy services amongst stable HIV patients in Zimbabwe; and tuberculosis preventive therapy for children in Eswatini.
Results
We highlight three key findings. First, understanding patient preferences is crucial when designing services, and providers sometimes underestimate behavioural barriers and overestimate the extent to which people are motivated simply by health benefits. Optimism is often driven by evidence showing high acceptability, but when preference structures are incorporated in intervention design, there are important insights into how patients plan to utilize services. Second, trade-offs matter in determining which characteristics are perceived to be most important to patients – a key strength of the DCE methodology. Understanding of these trade-offs can help prioritize which characteristics of interventions to target. Finally, disentangling the effect of different characteristics of service delivery models on preferences is important for rethinking how interventions are delivered. If services are designed to better align with preferences, implementers can ensure new interventions have the desired effect on health and economic outcomes.
Conclusions
These findings highlight the value of behavioural economic approaches for investigating preferences for health interventions and providing insights into the demand for services, which must feed into the HTA analyses. Incorporating DCEs into HTA is inexpensive and provides robust data for improving HTA.
Many individuals with first-episode psychosis experience severe and persistent social disability despite receiving specialist early intervention. The SUPEREDEN3 trial assessed whether augmenting early intervention in psychosis services with Social Recovery Therapy (SRT) would lead to better social recovery.
Aims:
A qualitative process evaluation was conducted to explore implementation and mechanisms of SRT impact from the perspective of SUPEREDEN3 participants.
Method:
A subsample of SUPEREDEN3 trial participants (n = 19) took part in semi-structured interviews, which were transcribed verbatim and analysed thematically. Trial participants were early intervention service users aged 16–35 years with severe and persistent social disability. Both SRT plus early intervention and early intervention alone arm participants were interviewed to facilitate better understanding of the context in which SRT was delivered and to aid identification of mechanisms specific to SRT.
Results:
The six themes identified were used to generate an explanatory model of SRT’s enhancement of social recovery. Participant experiences highlight the importance of the therapist cultivating increased self-understanding and assertively encouraging clients to face feared situations in a way that is perceived as supportive, while managing ongoing symptoms. The sense of achievement generated by reaching targets linked to personally meaningful goals promotes increased self-agency, and generates hope and optimism.
Conclusions:
The findings suggest potentially important processes through which social recovery was enhanced in this trial, which will be valuable in ensuring the benefits observed can be replicated. Participant accounts provide hope that, with the right support, even clients who have persistent symptoms and the most severe disability can make a good social recovery.
The transition from cardiopulmonary bypass (CPB) to normal circulation requires numerous mechanical, physiological and pharmacological factors to be coordinated efficiently within a short period of time. Weaning from CPB is often a routine process, however preexisting poor cardiac function or difficulties during the operation may make it complex and challenging. Complications encountered during the weaning phase may contribute to significant additional perioperative morbidity.
With increasing numbers of persons living with dementia and their higher rates of hospitalizations, it is necessary to ensure they receive appropriate and effective acute care; yet, acute care environments are often harmful for persons with dementia. There is a lack of dementia education for acute health care providers in Canada. Scotland presently delivers a dementia education program for health care providers, known as the Scottish National Dementia Champions Programme. The objective of this Policy and Practice Note is to present the collaborative work of Scottish experts and Canadian stakeholders to adapt the Dementia Champions Programme for use in Canada. This work to date includes: (a) an environmental scan of Canadian dementia education for acute health care providers; (b) key informant interviews; and, (c) findings from a two-day planning meeting. The results of this collaborative work can and are being used to inform the next steps to develop and pilot a Canadian dementia education program.
The article considers the global historiography of Europe from two angles. First it outlines the difficulties, both historical and epistemological, that Europe poses as an object of study, especially after the historiographical transformations prompted by the events of 1989, the rise of postcolonial studies, the growing critique of Eurocentrism, and, most recently, the “global turn.” The conceptions of Europe that emerge from these currents have often been based on a rather homogenized vision of the continent, centered on the great nation-states of western Europe and their imperial policies. They also perpetuate, even as they criticize it, the legacy of a conception of modernity that positions Europe as both its historical center and the agent of its expansion on a global scale. The second part of the paper proposes to limit the blind spots inherent in this kind of vision by shifting our gaze to the eastern and Balkan margins of Europe, where the Austro-Hungarian, Ottoman, and Russian empires intersected over the “long” nineteenth century. This change of perspective displaces the history of Europe’s connection to modernity, revealing the great diversity of local actors, the importance of multicultural and pluriethnic societies, and the particular role of transnational populations such as Jews, who, while negotiating their own relationship to a European modernity, escaped the grip of national movements.
Disclosing the truth when breaking bad news continues to be difficult for health professionals, yet it is essential for patients when making informed decisions about their treatment and end-of-life care. This literature review aimed to explore and examine how health professionals, patients, and families experience truth disclosure during the delivery of bad news in the inpatient/outpatient palliative care setting.
Methods
A systemized search for peer-reviewed, published papers between 2013 and 2020 was undertaken in September 2020 using the CINAHL, Medline, and PsycInfo databases. The keywords and MeSH terms (“truth disclosure”) AND (“palliative care or end-of-life care or terminal care or dying”) were used. The search was repeated using (“bad news”) AND (“palliative care or end-of-life care or terminal care or dying”) terms. A meta-synthesis was undertaken to synthesize the findings from the eight papers.
Results
Eight papers were included in the meta-synthesis and were represented by five Western countries. Following the synthesis process, two concepts were identified: “Enablers in breaking bad news” and “Truth avoidance/disclosure.” Several elements formed the concept of Enablers for breaking bad news, such as the therapeutic relationship, reading cues, acknowledgment, language/delivery, time/place, and qualities. A conceptual model was developed to illustrate the findings of the synthesis.
Significance of results
The conceptual model demonstrates a unique way to look at communication dynamics around truth disclosure and avoidance when breaking bad news. Informed decision-making requires an understanding of the whole truth, and therefore truth disclosure is an essential part of breaking bad news.
The Pinnacle3 Auto-Planning (AP) package is an automated inverse planning tool employing a multi-sequence optimisation algorithm. The nature of the optimisation aims to improve the overall quality of radiotherapy plans but at the same time may produce higher modulation, increasing plan complexity and challenging linear accelerator delivery capability.
Methods and materials:
Thirty patients previously treated with intensity-modulated radiotherapy (IMRT) to the prostate with or without pelvic lymph node irradiation were replanned with locally developed AP techniques for step-and-shoot IMRT (AP-IMRT) and volumetric-modulated arc therapy (AP-VMAT). Each case was also planned with VMAT using conventional inverse planning. The patient cohort was separated into two groups, those with a single primary target volume (PTV) and those with dual PTVs of differing prescription dose levels. Plan complexity was assessed using the modulation complexity score.
Results:
Plans produced with AP provided equivalent or better dose coverage to target volumes whilst effectively reducing organ at risk (OAR) doses. For IMRT plans, the use of AP resulted in a mean reduction in bladder V50Gy by 4·2 and 4·7 % (p ≤ 0·01) and V40Gy by 4·8 and 11·3 % (p < 0·01) in the single and dual dose level cohorts, respectively. For the rectum, V70Gy, V60Gy and V40Gy were all reduced in the dual dose level AP-VMAT plans by an average of 2·0, 2·7 and 7·3 % (p < 0·01), respectively. A small increase in plan complexity was observed only in dual dose level AP plans.
Findings:
The automated nature of AP led to high quality treatment plans with improvement in OAR sparing and minimised the variation in achievable dose planning metrics when compared to the conventional inverse planning approach.
Psychological attachment to political parties can bias people’s attitudes, beliefs, and group evaluations. Studies from psychology suggest that self-affirmation theory may ameliorate this problem in the domain of politics on a variety of outcome measures. We report a series of studies conducted by separate research teams that examine whether a self-affirmation intervention affects a variety of outcomes, including political or policy attitudes, factual beliefs, conspiracy beliefs, affective polarization, and evaluations of news sources. The different research teams use a variety of self-affirmation interventions, research designs, and outcomes. Despite these differences, the research teams consistently find that self-affirmation treatments have little effect. These findings suggest considerable caution is warranted for researchers who wish to apply the self-affirmation framework to studies that investigate political attitudes and beliefs. By presenting the “null results” of separate research teams, we hope to spark a discussion about whether and how the self-affirmation paradigm should be applied to political topics.
Background: Carbapenemase-producing Enterobacterales (CPE) have rapidly become a global health concern and are associated with substantial morbidity and mortality due to limited treatment options. Travel to endemic areas, especially healthcare exposure in these areas, is an important risk factor for acquisition. We describe the evolving epidemiology, molecular features, and outcomes of CPE in Canada through surveillance by the Canadian Nosocomial Infection Surveillance Program (CNISP). Methods: CNISP has conducted surveillance for CPE among inpatients and outpatients of all ages since 2010. Participating acute-care facilities submit eligible specimens to the National Microbiology Laboratory for detection of carbapenemase production, and epidemiological data are collected. Incidence rates per 10,000 patient days are calculated based on inpatient data. Results: In total, 59 CNISP hospitals in 10 Canadian provinces representing 21,789 beds and 6,785,013 patient days participated in this surveillance. From 2010 to 2018, 118 (26%) CPE-infected and 547 (74%) CPE-colonized patients were identified. Few pediatric cases were identified (n = 18). Infection incidence rates remain low and stable (0.02 per 10,000 patient days in 2010 to 0.03 per 10,000 patient days in 2018), and colonization incidence rates have increased by 89% over the surveillance period. Overall, 92% of cases were acquired in a healthcare facility: 61% (n = 278) in a Canadian healthcare facility and 31% (n = 142) in a healthcare facility outside Canada. Of the 8% of cases not acquired in a healthcare facility, 50% (16 of 32) reported travel outside of Canada in the 12 months prior to positive culture. The distribution of carbapenemases varied by region; New Delhi metallo-B-lactamase (NDM) was dominant (59%) in western Canada and Klebsiella pneumoniae carbapenemase (KPC) (66%) in central Canada. NDM and class D carbapenemase OXA-48 were more commonly identified among those who traveled outside of Canada, whereas KPC was more commonly identified among patients without travel. In addition, 30-day all-cause mortality was 14% (25 of 181) among CPE infected patients and 32% (14 of 44) among those with bacteremia. Conclusions: CPE rates remain low in Canada; however, national surveillance data suggest that the increase in CPE in Canada is now being driven by local nosocomial transmission as well as travel and healthcare within endemic areas. Changes in screening practices may have contributed to the increase in colonizations; however, these data are currently lacking and will be collected moving forward. These data highlight the need to intensify surveillance and coordinate infection control measures to prevent further spread of CPE in Canadian acute-care hospitals.
Funding: None
Disclosures:
Susy Hota reports contracted research for Finch Therapeutics. Allison McGeer reports funds to her institution for projects for which she is the principal investigator from Pfizer and Merck, as well as consulting fees from the following companies: Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.
The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
Methods:
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Results:
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Conclusions:
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
The National Centre for Pharmacoeconomics (NCPE) assesses the cost-effectiveness of new drugs for which reimbursement by the healthcare payer, the Health Service Executive (HSE), is sought in Ireland. This research aims to create a systematic approach for the NCPE review group (RG) to assess each of the cost-effectiveness models submitted by the applicant by creating cost-effectiveness model appraisal guidelines.
Methods
The RG consists of clinical, statistical and health economic expertise. In order to systematically appraise the HTA submission, which includes a cost-effectiveness model, clear guidelines on how each of the members of the RG can work together are required. The current members of the RG in the NCPE were given a draft of the guidelines created by the primary author, and additional feedback and testing was performed using the expert experience of the team. A version of the guidelines was tested for its usefulness.
Results
Three checklists were created. The purpose of the first checklist is to evaluate if the cost-effectiveness model works correctly. The second checklist ensures that each of the assumptions included in the HTA dossier are the same as those included in the cost-effectiveness model. The final checklist validates the assumptions used in the cost-effectiveness model to ensure they are reasonable and appropriate for decision making. The final version of the checklists were validated by choosing cost-effectiveness models with known errors and/or discrepancies and testing that the issues were captured by the checklists.
Conclusions
These guidelines are not an exhaustive list of checks that should be performed, but are presented as the minimum requirements for consideration to be included with each RG assessment of the corresponding HTA submission. The guidelines will be constantly updated as the process evolves over time. The cost-effectiveness models should follow the National Health Information and Quality Authority (HIQA) Guidelines for the Economic Evaluation of Health Technologies in Ireland.
A lasting legacy of the International Polar Year (IPY) 2007–2008 was the promotion of the Permafrost Young Researchers Network (PYRN), initially an IPY outreach and education activity by the International Permafrost Association (IPA). With the momentum of IPY, PYRN developed into a thriving network that still connects young permafrost scientists, engineers, and researchers from other disciplines. This research note summarises (1) PYRN’s development since 2005 and the IPY’s role, (2) the first 2015 PYRN census and survey results, and (3) PYRN’s future plans to improve international and interdisciplinary exchange between young researchers. The review concludes that PYRN is an established network within the polar research community that has continually developed since 2005. PYRN’s successful activities were largely fostered by IPY. With >200 of the 1200 registered members active and engaged, PYRN is capitalising on the availability of social media tools and rising to meet environmental challenges while maintaining its role as a successful network honouring the legacy of IPY.
Meaning and Purpose (MaP) therapy aims to enhance meaning-based coping through a life review that focuses on the value and worth of the person, key relationships, sources of fulfillment, roles, and future priorities in living life out fully. We sought to test the feasibility and acceptability of a six-session model of MaP therapy against a wait-list control cohort in a pilot study seeking effect sizes on measures of adaptation.
Method
We randomized patients with advanced cancer to MaP therapy or wait-list control, with measures administered at baseline and after 6–8 weeks. Wait-list patients could then crossover to receive therapy, with further measures collected postintervention. Adherence to the manualized model was sustained through weekly supervision and fidelity coding of recorded sessions. We used generalized estimating equations to control for baseline and any correlation of data.
Result
From 134 eligible participants, 57 (43%) consented, and 40 of 45 (89%) offered therapy completed 6 sessions. Key barriers to consenting patients were poor health (15 refusers and 4 withdrawals) and death intervened in 6 participants. MaP therapy generated adequate effect sizes in posttraumatic growth (new possibilities, appreciation of life, and personal strength) and life attitudes (choices and goal seeking) to permit calculation of power for a formal randomized, controlled trial.
Significance of results
Delivery of this model of existentially oriented therapy is feasible and acceptable to patients. A properly powered randomized controlled trial is justified to examine the efficacy of this intervention.