A Hospice Transitions Program for Patients in the Emergency Department.

Importance: Patients often visit the emergency department (ED) near the end of life. Their common disposition is inpatient hospital admission, which can result in a delayed transition to hospice care and, ultimately, an inpatient hospital death that may be misaligned with their goals of care. Objective: To assess the association of hospice use with a novel multidisciplinary hospice program to rapidly identify and enroll eligible patients presenting to the ED near end of life. Design, Setting, and Participants: This pre-post quality improvement study of a novel, multifaceted care transitions program involving a formalized pathway with email alerts, clinician training, hospice vendor expansion, metric creation, and data tracking was conducted at a large, urban tertiary care academic medical center affiliated with a comprehensive cancer center among adult patients presenting to the ED near the end of life. The control period before program launch was from September 1, 2018, to January 31, 2020, and the intervention period after program launch was from August 1, 2021, to December 31, 2022. Main Outcome and Measures: The primary outcome was a transition to hospice without hospital admission and/or hospice admission within 96 hours of the ED visit. Secondary outcomes included length of stay and in-hospital mortality. Results: This study included 270 patients (median age, 74.0 years [IQR, 62.0-85.0 years]; 133 of 270 women [49.3%]) in the control period, and 388 patients (median age, 73.0 years [IQR, 60.0-84.0 years]; 208 of 388 women [53.6%]) in the intervention period, identified as eligible for hospice transition within 96 hours of ED arrival. In the control period, 61 patients (22.6%) achieved the primary outcome compared with 210 patients (54.1%) in the intervention period (P < .001). The intervention was associated with the primary outcome after adjustment for age, race and ethnicity, primary payer, Charlson Comorbidity Index, and presence of a Medical Order for Life-Sustaining Treatment (MOLST) (adjusted odds ratio, 5.02; 95% CI, 3.17-7.94). In addition, the presence of a MOLST was independently associated with hospice transition across all groups (adjusted odds ratio, 1.88; 95% CI, 1.18-2.99). There was no significant difference between the control and intervention periods in inpatient length of stay (median, 2.0 days [IQR, 1.1-3.0 days] vs 1.9 days [IQR, 1.1-3.0 days]; P = .84), but in-hospital mortality was lower in the intervention period (48.5% [188 of 388] vs 64.4% [174 of 270]; P < .001). Conclusions and Relevance: In this quality improvement study, a multidisciplinary program to facilitate ED patient transitions was associated with hospice use. Further investigation is needed to examine the generalizability and sustainability of the program.

Identification of Faba bean genetic loci associated with quantitative resistance to the fungus Botrytis fabae, causal agent of chocolate spot.

Introduction: Chocolate spot, caused by the ascomycete fungus Botrytis fabae, is a devastating foliar disease and a major constraint on the quality and yield of faba beans (Vicia faba). The use of fungicides is the primary strategy for controlling the disease. However, high levels of partial genetic resistance have been identified and can be exploited to mitigate the disease. Methods: The partially resistant V. faba cultivar Maris Bead and susceptible Egyptian accession ig70726 were crossed, and a genetic mapping population of 184 individuals was genotyped in the F2 generation and screened for resistance to B. fabae infection in the F3, F5, and F6 generations in a series of field experiments. A high-density linkage map of V. faba containing 3897 DArT markers spanning 1713.7 cM was constructed. Results: Multiple candidate quantitative trait loci (QTLs) in 11 separate regions of the V. faba genome were identified; some on chromosomes 2, 3, and 6 overlapped with loci previously linked to resistance to Ascochyta leaf and pod blight caused by the necrotrophic fungus Ascochyta fabae. A transcriptomics experiment was conducted at 18 h post-inoculation in seedlings of both parents of the mapping population, identifying several differentially expressed transcripts potentially involved in early stage defence against B. fabae, including cell-wall associated protein kinases, NLR genes, and genes involved in metabolism and response to reactive oxygen species. Discussion: This study identified several novel candidate QTLs in the V. faba genome that contribute to partial resistance to chocolate spot, but differences between growing seasons highlighted the importance of multi-year phenotyping experiments when searching for candidate QTLs for partial resistance.

Pediatric anesthesia in Australia and New Zealand and health inequity among First Nations and Maori children.

Australia and New Zealand are two countries in the Southern Pacific region. They share many pediatric anesthesia similarities in terms of medical organizational systems, education, training, and research, however there are important differences between the two nations in relation to geography, the First Nations populations and the history of colonization. While the standards for pediatric anesthesia and the specialty training requirements are set by the Australian and New Zealand College of Anesthetists and the Society for Pediatric Anesthesia in New Zealand and Australia, colonization has created distinct challenges that each nation now faces in order to improve the anesthetic care of its pediatric population. Australia generally has a high standard of living and good access to health care; disparities exist for First Nations People and for those living in rural or remote areas. Two influences have shaped training within New Zealand over the past 40 years; establishment of a national children's hospital in 1990 and, more importantly, acknowledgement that the First Nations people of New Zealand (Maori) have suffered because of failure to recognize their rights consequent to establishing a partnership treaty between Maori and the British Crown in 1840. Health inequities among Maori in New Zealand and First Nations People in Australia have implications for the health system, culturally appropriate approaches to treatment, and the importance of having an appreciation of First Nations people's history and culture, language, family structure, and cultural safety. Trainees in both countries need to be adequately supported in these areas in order for the sub-specialty of pediatric anesthesia to develop further and improve the anesthetic and surgical outcomes of our children.

Something Lost and Something Gained: Navigating the Bedside Teaching Role as a Hospice and Palliative Medicine Educator.

Hospice and palliative medicine (HPM) educators must often give up the satisfaction of working one-on-one with patients, to allow learners the opportunity to practice key communication skills and form their own therapeutic bonds with patients. Though the loss of that primary relationship with patients may feel challenging, educators may find new opportunity for professional impact and satisfaction by investing in their relationship with learners. This case discussion explores the challenges of bedside teaching in HPM, including the educator's looser connection with patients, need to withhold their own communication skills, and decision of when to interject into a trainee-patient conversation. We then propose strategies to help educators find renewed professional fulfillment in the teacher-learner relationship. By partnering intentionally with learners before, during, and after shared visits, inviting informal reflection between encounters, and preserving independent clinical time, we believe educators may cultivate a more sustainable and meaningful clinical teaching practice.

Immunotherapy in mismatch repair-deficient metastatic colorectal cancer - Outcome and novel predictive markers.

BACKGROUND: This study aims to assess predictive markers for response to immunotherapy in dMMR/MSI-H metastatic colorectal cancer (mCRC) patients. MATERIALS AND METHODS: A study using two prospective cohorts from MD Anderson Cancer Center and Sheba Medical Center of consecutive patients with dMMR/MSI-H mCRC that were treated with immunotherapy between 2014-2022. Primary outcome was progression-free survival (PFS) and secondary outcome was overall response rate (ORR). Evaluated predictors included ECOG-PS score, RAS/BRAF status, single-agent versus doublet immunotherapy, metastatic sites, disease burden, and CEA levels prior to treatment initiation. Kaplan-Meier analysis and Cox proportional hazard regression model were used to analyze the effect of exposure variables on PFS. RESULTS: The study included 153 patients. Median follow-up time was 26 months (IQR 11-48). Median PFS was 51.6 months (95%CI 38.1-NR) and ORR was 58.1%. In a univariate analysis, male sex was associated with worse PFS with a HR of 1.67 (95% CI 1.00-2.79); Right-sided tumors were associated with improved PFS with a HR of 0.56 (95% CI 0.32-0.97); Liver or lung metastasis were associated with worse PFS with HRs of 2.35 (95%CI 1.43-3.88) and 2.30 (95%CI 1.31-4.04), respectively; ECOG-PS score ≥ 2, CEA levels ˃5 µg/L prior to treatment initiation and ≥ 3 metastatic sites were associated with worse PFS with HRs of 2.09 (95%CI 0.98-4.47), 2.23 (95%CI 1.30-3.81) and 3.11 (95%CI 1.61-6.03), respectively. Liver or lung metastasis remained significant in a multivariable model. CONCLUSIONS: Extent of disease (worse PFS with high CEA, poor ECOG-PS and ≥3 metastatic sites) and disease location (worse PFS with liver or lung metastasis and left sided tumor) were associated with immunotherapy outcome in dMMR/MSI-H mCRC.

Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination.

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3-51.9). After a median follow-up of 22.6 months (range, 0.3-71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control. SIGNIFICANCE: Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.

FGF23 directly inhibits osteoprogenitor differentiation in Dmp1-knockout mice.

Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal growth, and osteomalacia. Blocking FGF23 became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited in autosomal recessive hypophosphatemic rickets (ARHR). This study investigates the effects of Pi repletion and bone-specific deletion of Fgf23 on bone and mineral metabolism in the dentin matrix protein 1-knockout (Dmp1KO) mouse model of ARHR. At 12 weeks, Dmp1KO mice showed increased serum FGF23 and parathyroid hormone levels, hypophosphatemia, impaired growth, rickets, and osteomalacia. Six weeks of dietary Pi supplementation exacerbated FGF23 production, hyperparathyroidism, renal Pi excretion, and osteomalacia. In contrast, osteocyte-specific deletion of Fgf23 resulted in a partial correction of FGF23 excess, which was sufficient to fully restore serum Pi levels but only partially corrected the bone phenotype. In vitro, we show that FGF23 directly impaired osteoprogenitors' differentiation and that DMP1 deficiency contributed to impaired mineralization independent of FGF23 or Pi levels. In conclusion, FGF23-induced hypophosphatemia is only partially responsible for the bone defects observed in Dmp1KO mice. Our data suggest that combined DMP1 repletion and FGF23 blockade could effectively correct ARHR-associated mineral and bone disorders.

Bumblebee responses to variation in pollinator-attracting traits of Vicia faba flowers.

Adaptations that attract pollinators to flowers are central to the reproductive success of insect-pollinated plants, including crops. Understanding the influence of these non-rewarding traits on pollinator preference is important for our future food security by maintaining sufficient crop pollination. We have identified substantial variation in flower shape, petal size, corolla-tube length, petal spot size and floral volatile compounds among a panel of 30 genetically distinct lines of Vicia faba. Using this variation, we found that Bombus terrestris was able to distinguish between natural variation in petal spot size, floral volatile emissions and corolla-tube length. Foragers showed some innate preference for spotted flowers over non-spotted flowers and preferred shorter corolla-tube lengths over longer tubes. Our results suggest that some floral traits may have significant potential to enhance pollinator attraction to V. faba crops, particularly if paired with optimised rewards.

Endoscopic and imaging outcomes of PD-1 therapy in localised dMMR colorectal cancer.

BACKGROUND: Neoadjuvant immune checkpoint blockade (IO) is emerging as a therapeutic option for patients with deficient mismatch repair (dMMR) colorectal cancer (CRC) given high pathological response rates. The aim of the study was to characterise imaging and endoscopic response to IO. METHODS: A retrospective analysis of patients with localised dMMR CRC that received at least one cycle of neoadjuvant anti-PD-1 therapy was conducted. Endoscopy, imaging, and pathological outcomes were reviewed to determine response to treatment according to standardised criteria. RESULTS: Thirty-eight patients had received IO for the treatment of localised CRC (median eight cycles). Among evaluable cases (n = 31 for endoscopy and n = 34 for imaging), the best endoscopic response was complete response (CR) in 45% of cases, and the best radiographic response was CR in 23% of cases. Imaging CR rate after ≤4 cycles of IO (n = 1) was 6% compared to 44% after >4 IO cycles (n = 7). Among 28 patients with imaging and endoscopy available, a discrepancy in best response was noted in 15 (54%) cases. At a median follow-up of 28.2 months from IO start, 18 patients underwent surgical resection of which 11 (61%) had pathological CR (pCR). Despite pCR or no evidence of progression ≥6 months after completion of IO among non-operatively managed patients, 72% and 42% of patients had non-CR on imaging and endoscopy, respectively. CONCLUSIONS: Discrepancies between imaging and endoscopy are prevalent, and irregularities identified on these modalities can be identified despite pathological remission. Improved clinical response criteria are warranted.

Bone-derived C-terminal FGF23 cleaved peptides increase iron availability in acute inflammation.

Inflammation leads to functional iron deficiency by increasing the expression of the hepatic iron regulatory peptide hepcidin. Inflammation also stimulates fibroblast growth factor 23 (FGF23) production by increasing both Fgf23 transcription and FGF23 cleavage, which paradoxically leads to excess in C-terminal FGF23 peptides (Cter-FGF23), rather than intact FGF23 (iFGF23) hormone. We determined that the major source of Cter-FGF23 is osteocytes and investigated whether Cter-FGF23 peptides play a direct role in the regulation of hepcidin and iron metabolism in response to acute inflammation. Mice harboring an osteocyte-specific deletion of Fgf23 showed a ∼90% reduction in Cter-FGF23 levels during acute inflammation. Reduction in Cter-FGF23 led to a further decrease in circulating iron in inflamed mice owing to excessive hepcidin production. We observed similar results in mice showing impaired FGF23 cleavage owing to osteocyte-specific deletion of Furin. We next showed that Cter-FGF23 peptides bind members of the bone morphogenetic protein (BMP) family, BMP2 and BMP9, which are established inducers of hepcidin. Coadministration of Cter-FGF23 and BMP2 or BMP9 prevented the increase in Hamp messenger RNA and circulating hepcidin levels induced by BMP2/9, resulting in normal serum iron levels. Finally, injection of Cter-FGF23 in inflamed Fgf23KO mice and genetic overexpression of Cter-Fgf23 in wild type mice also resulted in lower hepcidin and higher circulating iron levels. In conclusion, during inflammation, bone is the major source of Cter-FGF23 secretion, and independently of iFGF23, Cter-FGF23 reduces BMP-induced hepcidin secretion in the liver.

Epidemiology of syphilis in the Nepean and Blue Mountains Local Health District between 1 October 2009 and 30 September 2019.

Background: Syphilis is a nationally notifiable sexually transmitted infection (STI). Rates of syphilis notifications have been on the increase in Australia. Given these increases, we wanted to study the epidemiological trends of syphilis notifications in the Nepean Blue Mountain Local Health District (NBMLHD) over a ten-year period across different healthcare settings. Methods: All syphilis notifications in residents in the NBMLHD in the ten-year period between 1 October 2009 and 30 September 2019 were included in the study. Separate analyses were performed for all syphilis notifications, as well as for infectious syphilis and for syphilis acquired > 2 years ago or of unknown duration. We described age distribution and demographic profile and risk factors of all syphilis notifications. Notification trends were studied and crude incidence rates were calculated. Notifications were stratified by stage of syphilis, sex, and geographical location. Results: In the study duration, a total of 342 notifications of syphilis were received. Of these, 187 were infectious syphilis and 155 were related to infections acquired > 2 years ago and/or of unknown duration. The majority of notifications were in men: 281 (82%). Overall, syphilis notifications increased over the ten-year study period. The crude incidence rates for infectious syphilis were significantly higher in the second five-year period overall (7.78/100,000 population per year compared to 5.28/100,000 population per year; incidence rate ratio (IRR): 1.47; 95% confidence interval (95% CI): 1.10-1.97; p < 0.01), as well as for males (14.44/100,000 population per year compared to 9.7/100,000 population per year; IRR: 1.49; 95% CI: 1.09-2.03; p < 0.01). There were significant increases in syphilis notifications in males < 35 years of age, from 39 such notifications in the first five-year period (27.5% of all syphilis notifications in this period) to 83 notifications in the second five-year period (42.1% of all notifications in this period), p < 0.05. Conclusion: In keeping with national trends, notifications in our study increased. Significant increases were noted in notifications among males under 35 years of age. This supports the continued investment in sexual health promotion activities aimed at young sexually active men. Expansion of screening activities to include women and older people would help detect any increase in cases in these groups. Increase in engagement with general practitioners will support them to provide opportunistic STI screens to sexually-active attendees. National screening recommendations remain applicable to this population.

Neoadjuvant Pembrolizumab in Localized Microsatellite Instability High/Deficient Mismatch Repair Solid Tumors.

PURPOSE: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space. METHODS: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response rate and organ-sparing at one year for patients who declined surgery. Exploratory analyses include interrogation of the tumor immune microenvironment using imaging mass cytometry. RESULTS: A total of 35 patients were enrolled, including 27 patients with colorectal cancer and eight patients with noncolorectal cancer. Among 33 evaluable patients, best overall response rate was 82%. Among 17 (49%) patients who underwent surgery, the pathologic complete response rate was 65%. Ten patients elected to receive one year of pembrolizumab followed by surveillance without surgical resection (median follow-up of 23 weeks [range, 0-54 weeks]). An additional eight did not undergo surgical resection and received less than 1 year of pembrolizumab. During the study course of the trial and subsequent follow-up, progression events were seen in six patients (four of whom underwent salvage surgery). There were no new safety signals. Spatial immune profiling with imaging mass cytometry noted a significantly closer proximity between granulocytic cells and cytotoxic T cells in patients with progressive events compared with those without progression. CONCLUSION: Neoadjuvant pembrolizumab in dMMR/MSI-H cancers is safe and resulted in high rates of pathologic, radiographic, and endoscopic response, which has implications for organ-sparing strategies.

Caring for People We Know: An Unrecognized Risk for Burnout?

Background: As the field of palliative care continues to grow, many clinicians will care for patients with whom they have personal connections. Breaching the boundary between a clinician's personal and professional life is potentially an unrecognized risk for burnout. Objective: We explored the challenges of caring for patients personally known to clinicians and the types of support needed, with a view to developing preliminary practice guidelines. Design: Focus groups. Setting/Subjects: Thirteen psychosocial oncology and palliative care clinicians who care for adult patients participated in one of two focus groups. Six participants were physicians, four were nurse practitioner/registered nurse/physician assistant (NP/RN/PAs), and three were psychosocial clinicians. Measurement: Using NVivo 12, we analyzed focus group transcripts from clinicians about their experiences caring for patients they know personally, the impact of such experiences, and the type of support and guidelines that could benefit clinicians in these unique situations. Results: Navigating boundaries and managing the psychological impact on the clinician, including fear of negative evaluation, increased anxiety and emotional exhaustion were the most challenging aspects of providing such care. Suggested guidelines include an early team meeting, a buddy system, a conversation guide to address the dual relationship, and embedded psychological support and mentorship. Conclusions: Feedback from clinicians identified preliminary guidelines that incorporate tools palliative care teams can use to improve support for clinicians caring for patients with whom they have a personal connection. These tools address the psychosocial aspects of care and have the potential to help clinicians feel a greater sense of control in these often, challenging and emotionally taxing situations.

Gangrenous Hydrosalpinx with Isolated Fallopian Tube Torsion in Premenarchal Child.

Hydrosalpinx induced torsion of the adnexa in a premenarchal child without sexual experience is a rare situation and immediate intervention is necessary. This report describes a 10-year old premenarchal female without a history of sexual intercourse who presented with left lower abdominal pain. Ultrasound imaging revealed a left adnexa with thick-walled cystic lesion measuring 5.1 × 3.7 × 2.7 cm suggestive of hydrosalpinx or para ovarian cyst. Diagnostic laparoscopic surgery showed ischaemic tubular shaped cystic left hydrosalpinx that was twisted along its own axis at the level of isthmus. Laparoscopic left salpingectomy was performed within 24 h of presentation leaving behind a healthy left ovary. Early diagnosis is important in preventing further complications including severe infection and peritonitis and to prevent complications that might affect fertility.

'Single-handed care' initiatives and reviews of double-handed homecare packages: A survey of practices in English local authorities with adult social care responsibilities.

International health and social care systems are experiencing unprecedented pressure and demand. 'Single-handed care' initiatives seek to identify whether all or part of a homecare package involving more than one care worker can be safely reduced to a single worker. Little is known about these initiatives across local authorities. The aim of this study was to identify, describe and explain current processes and practices for single-handed care initiatives and double-handed homecare reviews. An electronic survey link was sent to each local authority with social care responsibilities in England. The questions covered a range of areas in relation to single-handed care processes and included a combination of pre-coded and free-text responses. Responses were received from 76 (50%) local authorities. Findings were that over 12,000 reviews were reported within a year with a median of 141 (IQR 45-280) from 53 authorities that provided figures. Reviews were usually led by a local authority occupational therapist. On average, 540 min was spent per review, including conducting and organising the review, documentation, and travel. In nearly half the authorities, double handed care remained at least partially in place following at least 80% of the reviews and remained wholly in place following at least 60%. Local authorities also reported some resistance from homecare providers when implementing single-handed care. The findings have confirmed anecdotal evidence that reviews of double-handed homecare packages are common practice within local authorities. Given the amount of time taken with these reviews, and paucity of evidence on outcomes for people receiving them, further research should evaluate this.

Phase II study of durvalumab (anti-PD-L1) and trametinib (MEKi) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

BACKGROUND: Monotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells. METHODS: Open-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126). T is 2 mg/day orally starting 1 week prior to D, which is given 1500 mg intravenously every 4 weeks. Simon 2-stage design used to enroll 29 pts into first stage, requiring a response in two or more pts to proceed to stage 2. Tumor biopsies were collected at baseline (BL) and early on-treatment (OT) at week 4. RESULTS: Twenty nine treated pts include 48% females, median age 48 years (range 28-75), and median prior therapies 2 (range 1-5). No grade (G) 4 or 5 treatment-related adverse events (TRAE). The most common TRAE of any grade was acneiform rash, 17% being G3. One of 29 pts had confirmed partial response (PR) lasting 9.3 months (mo) for an overall response rate of 3.4%. Seven pts had stable disease (SD) and five pts (1 PR, 4 SD) demonstrated decrease in total carcinoembryonic antigen ng/mL (best percentage reduction: 94%, 95%, 42%, 34%, and 22%, respectively). Median progression-free survival was 3.2 mo (range 1.1-9.3 months). Three pts with both liver and lung metastases demonstrated discrepant responses in which clinical benefit was present in the lung metastases but not liver metastases. Comparison of BL and 4-week OT tumor tissue flow cytometry demonstrated no changes in T-cell infiltration but upregulation expression of PD-1 and Tim3 on CD8 T cells. However, expression of PD-1 and Tim3 as single markers and as coexpressed markers was observed to increase OT relative to BL (p=0.03, p=0.06 and p=0.06, respectively). CONCLUSIONS: T+D demonstrated acceptable tolerability in pts with refractory MSS mCRC. The response rate in the first stage of the study did not meet efficacy criteria to proceed to the second stage. Specific site of metastatic disease may impact outcomes in novel immunotherapy combination trials. TRIAL REGISTRATION NUMBER: NCT03428126.

Undertaking a research project improves confidence in research skills among student dietitians.

BACKGROUND: Research is a cornerstone of evidence-based dietetic practice. Research skills are often taught at university through experiential learning during a final-year research project. The present study aimed to investigate attitudes towards research and confidence in research skills among student dietitians before and after a research project. METHODS: A questionnaire survey of student dietitians' attitudes to research and confidence in research skills was undertaken before and after completing a research project at two universities in London, UK. Dichotomous data were compared before and after the research project using a McNemar's test. Factors associated with 'high confidence' or 'improved confidence' in overall research skills at the end of the research project were investigated using multivariable logistic regression. RESULTS: In total, 160 student dietitians completed a questionnaire before and after their research project. The majority had positive attitudes to research both before and after their research project. There was an increase in numbers with 'high confidence' in overall research skills before (13; 8.1%) and after (79; 49.4%) the research project (p < 0.001), and 113 (70.6%) reported 'improved confidence' in overall research skills. The only factor associated with 'high confidence' in overall research skills was having 'high levels of involvement in the overall research process' (odds ratio = 6.13, 95% confidence interval = 2.03-18.49, p = 0.001). CONCLUSIONS: Student dietitians have positive attitudes towards research and undertaking a research project significantly improves confidence in their research skills. A higher level of involvement in the research project is the single most significant factor associated with high confidence in research skills.

How US newspapers view the UK's NHS: a study in international lesson-drawing.

Healthcare on both sides of the Atlantic is a highly charged political and economic subject. This work considers US media coverage of the UK's National Health Service (NHS), an under-researched area. We assess the framing of the NHS in editorials, opinion and feature articles during the time of the Obama administration to show how media can perform the role of lesson-drawing, a theory adopted from public policy research. The study also applies the notion of journalistic habitus in this context. Using these ideas, we address a hypothesis which holds that US coverage is framed around the flaws of the UK's NHS. The paper considers how intermedia editorial and news values operate, with commentators drawing a range of negative lessons in both the Democrat- and Republican-supporting press. We find that the NHS was often posited as a flawed international variant of the single-payer model, where newspapers employed an ahistoric explanation of failure and decline.