Enhanced supportive care: prospective cohort study of oncology patients and caregivers.

OBJECTIVES: A prospective cohort study to evaluate clinical effectiveness of the enhanced supportive care (ESC) service at a comprehensive cancer centre and to explore the impact of the service on patient and caregiver outcomes and experience. METHODS: Patients who received care under the ESC service and their caregivers were eligible. Consented patients (n=184) and caregivers (n=67) completed questionnaires at baseline, 4 weeks and 8 weeks post-ESC. Patient questionnaires assessed quality of life (QOL), symptoms, experience of ESC and health service use. Caregiver questionnaires included QOL and needs assessment. Selected patients (n=13) participated in qualitative interviews. Quantitative analysis explored differences in questionnaire responses over time (p<0.05). Qualitative data were analysed thematically. RESULTS: Patient quantitative data showed improvements in QOL (p=0.004 for European Quality of Life Questionnaire 5 dimensions (EQ5D) health index scores) and anxiety (p=0.006) at 4 weeks, reduction in some symptoms (pain p=0.02 at 4 weeks), improvement in self-efficacy, an increase in problems being addressed and a decrease in health service use (reduction in outpatient appointments). Qualitative findings suggested patients were generally satisfied with the ESC service but identified areas for improvement such as increased awareness of ESC and earlier referral. Fewer improvements were noted for caregivers; however, they did report a decrease in unmet needs. CONCLUSION: The ESC service had a positive impact on various patient-reported and caregiver-reported outcomes. There were also positive impacts on health service use. Increasing awareness of ESC and engaging patients at an earlier stage in the disease trajectory may further improve patient satisfaction and outcomes.

Association of Electronic Self-Scheduling and Screening Mammogram Completion.

INTRODUCTION: The purpose of this study was to evaluate if an electronic health record (EHR) self-scheduling function was associated with changes in mammogram completion for primary care patients who were eligible for a screening mammogram using U.S. Preventive Service Task Force recommendations. METHODS: This was a retrospective cohort study (September 1, 2014-August 31, 2019, analyses completed in 2022) using a difference-in-differences design to examine mammogram completion before versus after the implementation of self-scheduling. The difference-in-differences estimate was the interaction between time (pre-versus post-implementation) and group (active EHR patient portal versus inactive EHR patient portal). The primary outcome was mammogram completion among all eligible patients, with completion defined as receiving a mammogram within 6 months post-visit. The secondary outcome was mammogram completion among patients who received a clinician order during their visit. RESULTS: The primary analysis included 35,257 patient visits. The overall mammogram completion rate in the pre-period was 22.2% and 49.7% in the post-period. EHR self-scheduling was significantly associated with increased mammogram completion among those with an active EHR portal, relative to patients with an inactive portal (adjusted difference 13.2 percentage points [95% CI 10.6-15.8]). For patients who received a clinician mammogram order at their eligible visit, self-scheduling was significantly associated with increased mammogram completion among patients with an active EHR portal account (adjusted difference 14.7 percentage points, [95% CI 10.9-18.5]). CONCLUSIONS: EHR-based self-scheduling was associated with a significant increase in mammogram completion among primary care patients. Self-scheduling can be a low-cost, scalable function for increasing preventive cancer screenings.

Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.

INTRODUCTION: Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future. METHODS: A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: "adoptive cell therapy", "patient-reported outcomes" and "cancer". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated. RESULTS: One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months. DISCUSSION: None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.

Activity-dependent tau cleavage by caspase-3 promotes neuronal dysfunction and synaptotoxicity.

Tau-mediated toxicity is associated with cognitive decline and Alzheimer's disease (AD) progression. In particular, tau post-translational modifications (PTMs) are thought to generate aberrant tau species resulting in neuronal dysfunction. Despite being well characterized in postmortem AD brain, it is unclear how caspase-mediated C-terminal tau cleavage promotes neurodegeneration, as few studies have developed the models to dissect this pathogenic mechanism. Here, we show that proteasome impairment results in cleaved tau accumulation at the post-synaptic density (PSD), a process that is modulated by neuronal activity. Cleaved tau (at residue D421) impairs neuronal firing and causes inefficient initiation of network bursts, consistent with reduced excitatory drive. We propose that reduced neuronal activity, or silencing, is coupled to proteasome dysfunction, which drives cleaved tau accumulation at the PSD and subsequent synaptotoxicity. Our study connects three common themes in the progression of AD: impaired proteostasis, caspase-mediated tau cleavage, and synapse degeneration.

Methylphenidate Reversal of Executive Dysfunction in a Patient with Bi-Frontal Lobe Glioblastoma.

An elderly man with advanced glioblastoma developed neuro-cognitive deficits that were reversed by methylphenidate. After tumor resection from the right frontal lobe, he received cranial irradiation, temozolomide and Tumor Treating Fields (TTFields). MRI afterwards showed enhancements near the resection cavity and the contralateral frontal lobe. The patient experienced mild executive dysfunction that was not limiting his activities. Adjuvant temozolomide was started along with TTFields. After 2 cycles, his brain MRI showed stable disease, but he exhibited significant executive dysfunction. Methylphenidate improved his neuro-cognitive slowing in cycles 3 and 4. His disease eventually progressed during the 5th cycle, and he experienced a marked decline in activities. Repeat head MRI revealed tumor progression and cerebral edema. Treatments were discontinued while dexamethasone improved his neurological functions and bevacizumab biosimilar was later added. This case demonstrates the activity of methylphenidate for managing executive dysfunction in patients with glioblastoma while minimizing the use of dexamethasone.

Prognostic value of patient-reported outcome measures (PROMs) in adults with non-small cell Lung Cancer: a scoping review.

BACKGROUND: There is growing interest in the collection and use of patient-reported outcome measures (PROMs) to support clinical decision making in patients with non-small cell lung cancer (NSCLC). However, an overview of research into the prognostic value of PROMs is currently lacking. AIM: To explore to what extent, how, and how robustly the value of PROMs for prognostic prediction has been investigated in adults diagnosed with NSCLC. METHODS: We systematically searched Medline, Embase, CINAHL Plus and Scopus for English-language articles published from 2011 to 2021 that report prognostic factor study, prognostic model development or validation study. Example data charting forms from the Cochrane Prognosis Methods Group guided our data charting on study characteristics, PROMs as predictors, predicted outcomes, and statistical methods. Two reviewers independently charted the data and critically appraised studies using the QUality In Prognosis Studies (QUIPS) tool for prognostic factor studies, and the risk of bias assessment section of the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for prognostic model studies. RESULTS: Our search yielded 2,769 unique titles of which we included 31 studies, reporting the results of 33 unique analyses and models. Out of the 17 PROMs used for prediction, the EORTC QLQ-C30 was most frequently used (16/33); 12/33 analyses used PROM subdomain scores instead of the overall scores. PROMs data was mostly collected at baseline (24/33) and predominantly used to predict survival (32/33) but seldom other clinical outcomes (1/33). Almost all prognostic factor studies (26/27) had moderate to high risk of bias and all four prognostic model development studies had high risk of bias. CONCLUSION: There is an emerging body of research into the value of PROMs as a prognostic factor for survival in people with NSCLC but the methodological quality of this research is poor with significant bias. This warrants more robust studies into the prognostic value of PROMs, in particular for predicting outcomes other than survival. This will enable further development of PROM-based prediction models to support clinical decision making in NSCLC.