Oncology clinic-based germline genetic testing for exocrine pancreatic cancer enables timely return of results and unveils low uptake of cascade testing

2021 ◽  
pp. jmedgenet-2021-108054
Author(s):  
Yifan Wang ◽  
Bryn Golesworthy ◽  
Adeline Cuggia ◽  
Celine Domecq ◽  
Prosanto Chaudhury ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Point Of Care ◽  
Susceptibility Genes ◽  
Return Of Results ◽  
Clinical Criteria ◽  
Cascade Testing ◽  
Ambulatory Oncology ◽  
The Impact ◽  
Exocrine Pancreatic Cancer

BackgroundTraditional medical genetics models are unable to meet the growing demand for germline genetic testing (GT) in patients with exocrine pancreatic cancer (PC). This study investigates the impact of an ambulatory oncology clinic-based GT model.MethodsFrom 2012 to 2021, patients with PC were prospectively enrolled and considered for GT. Two chronological cohorts were compared: (1) the preuniversal genetic testing (pre-UGT) cohort, which received GT based on clinical criteria or family history; and (2) the post-UGT cohort, where an 86-gene panel was offered to all patients with PC.ResultsOf 847 eligible patients, 735 (86.8%) were enrolled (pre-UGT, n=579; post-UGT, n=156). A higher proportion of the post-UGT cohort received prospective GT (97.4% vs 58.5%, p<0.001). The rate of pathogenic germline alterations (PGA) across both cohorts was 9.9%, with 8.0% of PGAs in PC susceptibility genes. The post-UGT cohort had a higher prevalence of overall PGAs (17.2% vs 6.6%, p<0.001) and PGAs in PC susceptibility genes (11.9% vs 6.3%, p<0.001). The median turnaround time from enrolment to GT report was shorter in the post-UGT cohort (13 days vs 42 days, p<0.001). Probands with a PGA disclosed their GT results to 84% of their first-degree relatives (FDRs). However, only 31% of informed FDRs underwent GT, and the number of new cases per index case was 0.52.ConclusionA point-of-care GT model is feasible and expedites access to GT for patients with PC. Strategies to increase the uptake of cascade testing are needed to maximise the clinical impact of an oncology clinic-based GT model.

scholarly journals The role of point-of-care ultrasound in the diagnosis of pericardial effusion: a single academic center retrospective study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Matthew G. Hanson ◽  
Barry Chan
Keyword(s):  
Pericardial Effusion ◽  
Point Of Care ◽  
Physical Exam ◽  
Right Atrial ◽  
Point Of Care Ultrasound ◽  
X Ray ◽  
Average Systolic Blood Pressure ◽  
Time To Diagnosis ◽  
Clinically Significant ◽  
The Impact

Abstract Background Symptomatic pericardial effusion (PCE) presents with non-specific features and are often missed on the initial physical exam, chest X-ray (CXR), and electrocardiogram (ECG). In extreme cases, misdiagnosis can evolve into decompensated cardiac tamponade, a life-threatening obstructive shock. The purpose of this study is to evaluate the impact of point-of-care ultrasound (POCUS) on the diagnosis and therapeutic intervention of clinically significant PCE. Methods In a retrospective chart review, we looked at all patients between 2002 and 2018 at a major Canadian academic hospital who had a pericardiocentesis for clinically significant PCE. We extracted the rate of presenting complaints, physical exam findings, X-ray findings, ECG findings, time-to-diagnosis, and time-to-pericardiocentesis and how these were impacted by POCUS. Results The most common presenting symptom was dyspnea (64%) and the average systolic blood pressure (SBP) was 120 mmHg. 86% of people presenting had an effusion > 1 cm, and 89% were circumferential on departmental echocardiogram (ECHO) with 64% having evidence of right atrial systolic collapse and 58% with early diastolic right ventricular collapse. The average time-to-diagnosis with POCUS was 5.9 h compared to > 12 h with other imaging including departmental ECHO. Those who had the PCE identified by POCUS had an average time-to-pericardiocentesis of 28.1 h compared to > 48 h with other diagnostic modalities. Conclusion POCUS expedites the diagnosis of symptomatic PCE given its non-specific clinical findings which, in turn, may accelerate the time-to-intervention.

scholarly journals Exercise efficacy and prescription during treatment for pancreatic ductal adenocarcinoma: a systematic review

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dominic O’Connor ◽  
Malcolm Brown ◽  
Martin Eatock ◽  
Richard C. Turkington ◽  
Gillian Prue
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Physical Function ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
Key Stakeholders ◽  
The Impact

Abstract Background Surgical resection remains the only curative treatment for pancreatic cancer and is associated with significant post-operative morbidity and mortality. Patients eligible for surgery, increasingly receive neo-adjuvant therapy before surgery or adjuvant therapy afterward, inherently exposing them to toxicity. As such, optimizing physical function through exercise during treatment remains imperative to optimize quality of life either before surgery or during rehabilitation. However, current exercise efficacy and prescription in pancreatic cancer is unknown. Therefore, this study aims to summarise the published literature on exercise studies conducted in patients with pancreatic cancer undergoing treatment with a focus on determining the current prescription and progression patterns being used in this population. Methods A systematic review of four databases identified studies evaluating the effects of exercise on aerobic fitness, muscle strength, physical function, body composition, fatigue and quality of life in participants with pancreatic cancer undergoing treatment, published up to 24 July 2020. Two reviewers independently reviewed and appraised the methodological quality of each study. Results Twelve studies with a total of 300 participants were included. Heterogeneity of the literature prevented meta-analysis. Exercise was associated with improvements in outcomes; however, study quality was variable with the majority of studies receiving a weak rating. Conclusions High quality evidence regarding the efficacy and prescription of exercise in pancreatic cancer is lacking. Well-designed trials, which have received feedback and input from key stakeholders prior to implementation, are required to examine the impact of exercise in pancreatic cancer on key cancer related health outcomes.

#61: Antibiotic Use for Community-Acquired Pneumonia Among Hospitalized Children in Japan

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S13-S13
Author(s):  
Chiaki Tao-Kidoguchi ◽  
Eiki Ogawa ◽  
Kensuke Shoji ◽  
Isao Miyairi
Keyword(s):  
Physician Behavior ◽  
Point Of Care ◽  
Descriptive Analysis ◽  
Antibiotic Use ◽  
Community Acquired Pneumonia ◽  
Clinical Criteria ◽  
Focus Of Infection ◽  
Tract Infections ◽  
Short Courses ◽  
Viral Etiologies

Abstract Background Judicious use of antimicrobials is the cornerstone of action against antimicrobial resistance. Respiratory tract infections account for over 80% of pediatric antibiotic use in Japan. Antibiotics are generally used empirically for most hospitalized patients with pneumonia although it is becoming clearer that viral etiologies account for approximately 70% of these cases. Defining the characteristics of patients who are managed with a short course of antibiotics and subsequently do well, may lead to setting clinical criteria for early termination of antibiotics. Methods We performed a retrospective descriptive analysis. Medical charts of patients aged 3 months to 18 years, who were admitted with a diagnosis of pneumonia, bronchitis, bronchiolitis, or asthma to the Department of Interdisciplinary medicine at the National Center for Child Health and Development from March 2018 through February 2019 were reviewed. Those who had respiratory symptoms and were started on antibiotics within 48 hours of hospitalization were included. Those who had a focus of infection elsewhere or were immunocompromised were excluded. Results Of the 556 candidates, 80 patients met the criteria. The median age was 1.5 years which included 42.5% (34/80) with comorbidities. Underlying conditions included 9 with trisomy 21, and 8 with perinatal issues. Rapid antigen testing was performed and 7 patients with RSV, 5 patients with influenza, 1 patient with human metapneumovirus were identified. The average duration of antibiotic therapy was 7.2 days (range 2–14 days). There were no statistical differences in the characteristics of patients who received antibiotics for more or less than 5 days. The positivity of the rapid antigen test tended to be higher in those who received antibiotics for a shorter period (25% vs. 15%). There were no differences in the rate of readmission or complications between the two groups. Conclusion We were unable to identify a clear characteristic of patients who received short courses of antibiotics for pneumonia. The trend observed for those who had a point of care testing may suggest that the use of a multiplex PCR testing covering a greater number of pathogens would influence physician behavior in antibiotic use.

scholarly journals Feasibility and Assessment of a Cascade Traceback Screening Program (FACTS): Protocol for a Multisite Study to Implement and Assess an Ovarian Cancer Traceback Cascade Testing Program

2021 ◽  
Vol 11 (6) ◽  
pp. 543
Author(s):  
Anna DiNucci ◽  
Nora B. Henrikson ◽  
M. Cabell Jonas ◽  
Sundeep Basra ◽  
Paula Blasi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Health Care Providers ◽  
Screening Program ◽  
Qualitative Interviews ◽  
Care Providers ◽  
Genetic Privacy ◽  
Program Outcomes ◽  
Cascade Testing ◽  
Program Costs

Ovarian cancer (OVCA) patients may carry genes conferring cancer risk to biological family; however, fewer than one-quarter of patients receive genetic testing. “Traceback” cascade testing —outreach to potential probands and relatives—is a possible solution. This paper outlines a funded study (U01 CA240747-01A1) seeking to determine a Traceback program’s feasibility, acceptability, effectiveness, and costs. This is a multisite prospective observational feasibility study across three integrated health systems. Informed by the Conceptual Model for Implementation Research, we will outline, implement, and evaluate the outcomes of an OVCA Traceback program. We will use standard legal research methodology to review genetic privacy statutes; engage key stakeholders in qualitative interviews to design communication strategies; employ descriptive statistics and regression analyses to evaluate the site differences in genetic testing and the OVCA Traceback testing; and assess program outcomes at the proband, family member, provider, system, and population levels. This study aims to determine a Traceback program’s feasibility and acceptability in a real-world context. It will account for the myriad factors affecting implementation, including legal issues, organizational- and individual-level barriers and facilitators, communication issues, and program costs. Project results will inform how health care providers and systems can develop effective, practical, and sustainable Traceback programs.

scholarly journals 1138. Script for Pediatrics: Creating a Smartphone Application to Improve Antimicrobial Prescribing

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S405-S405
Author(s):  
Sarah Primhak ◽  
Natasha Pool ◽  
Gayl Humphrey ◽  
Lesley Voss ◽  
Rachel H Webb ◽  
...  
Keyword(s):  
Decision Making ◽  
Antimicrobial Stewardship ◽  
Point Of Care ◽  
Smartphone Application ◽  
Antibiotic Prescribing ◽  
Oral Antibiotic ◽  
Duration Of Treatment ◽  
Antibiotic Allergy ◽  
Alternative Agent ◽  
The Impact

Abstract Background When considering antimicrobial stewardship (AMS) interventions, pediatrics is an important and often overlooked group. By 5 years of age, 97% of New Zealand (NZ) children have received antibiotics (median 8 antibiotic courses/child). Prescribing is complex due to age and weight-based adjustments, unpalatable oral preparations and inappropriate allergy labeling. Our tertiary Children’s Hospital has >250 web-based nationally utilized guidelines, 15% including antimicrobials. A point prevalence audit showed only 63% guideline adherence for inpatient antimicrobial prescriptions. We designed an accessible app to bring antibiotic prescribing and antibiotic allergy decision-making to prescribers at point of care. Methods Using local hospital and community guidelines, the national formulary and in consultation with subspecialist teams, 31 algorithms were developed. Each algorithm asked questions including diagnosis, age, antibiotic allergy history and known colonization with-resistant organisms. Results The smartphone app (Script) uses the algorithms to advise on appropriate antimicrobial, dose, route and duration of treatment. Advice regarding IV-oral switch parameters and oral antibiotic choice is provided. If allergy is suspected symptom-based decision-making enables the user to choose an alternative agent or encourages allergy de-labeling. Further AMS occurs in some algorithms when advice is given not to prescribe antimicrobials. Conclusion Script for Pediatrics launched in NZ in March 2019 with >1000 users in the first 6 weeks. The most frequently accessed guidelines are otitis media, pneumonia and meningitis. Smartphone applications with local relevance and the ability to update in real-time may prove important tools, by providing easily accessible and intuitive advice to help support antimicrobial stewardship activities. This intervention has been rapidly adopted by pediatric hospital prescribers. The impact on prescribing in concordance with guidelines, timely intravenous to oral antibiotic switch and allergy de-labeling will be assessed. Disclosures All authors: No reported disclosures.

scholarly journals Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Paulo L. Pfitzinger ◽  
Laura Fangmann ◽  
Kun Wang ◽  
Elke Demir ◽  
Engin Gürlevik ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Tumor Stage ◽  
Ache Inhibitors ◽  
Impact On Survival ◽  
The Impact ◽  
Ache Expression ◽  
Cholinergic Activation

Abstract Background Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. Methods We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/−physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. Results We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. Conclusion For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.

scholarly journals The Impact of Changing to an Algorithm-Based Clostridioides difficile Test on the Decision to Treat Clostridioides difficile

2020 ◽  
Vol 41 (S1) ◽  
pp. s407-s407
Author(s):  
Lana Dbeibo ◽  
Joy Williams ◽  
Josh Sadowski ◽  
William Fadel ◽  
Vera Winn ◽  
...  
Keyword(s):  
Critical Care ◽  
Toxic Megacolon ◽  
Adverse Outcomes ◽  
Clinical Criteria ◽  
Testing Method ◽  
Clostridioides Difficile ◽  
Critical Care Admission ◽  
The Impact ◽  
Test Result ◽  
Pcr Test

Background: Polymerase chain reaction (PCR) testing for the diagnosis of Clostridioides difficile infection (CDI) detects the presence of the organism; a positive result therefore cannot differentiate between colonization and the pathogenic presence of the bacterium. This may result in overdiagnosis, overtreatment, and risking disruption of microbial flora, which may perpetuate the CDI cycle. Algorithm-based testing offers an advantage over PCR testing as it detects toxin, which allows differentiation between colonization and infection. Although previous studies have demonstrated the clinical utility of this testing algorithm in differentiating infection from colonization, it is unknown whether the test changes CDI treatment decisions. Our facility switched from PCR to an algorithm-based testing method for CDI in June 2018. Objective: In this study, we evaluated whether clinicians’ decisions to treat patients are impacted by a test result that implies colonization (GDH+/Tox−/PCR+ test), and we examined the impact of this decision on patient outcomes. Methods: This is a retrospective cohort study of inpatients with a positive C. diff test between June 2017 and June 2019. The primary outcome was the proportion of patients treated for CDI. We compared this outcome in 3 groups of patients: those with a positive PCR test (June 2017–June 2018), those who had a GDH+/Tox−/PCR+ or a GDH+/Tox+ test result (June 2018–June 2019). Secondary outcomes included toxic megacolon, critical care admission, and mortality in patients with GDH+/Tox−/PCR+ who were treated versus those who were untreated. Results: Of patients with a positive PCR test, 86% were treated with CDI-specific antibiotics, whereas 70.4% with GDH+/Tox+ and 29.25% with GDH+/Tox−/PCR+ result were treated (P < .0001). Mortality was not different between patients with GDH+/Tox−/PCR+ who were treated versus those who were untreated (2.7% vs 3.4%; P = .12), neither was critical care admission within 2 or 7 days of test result (2% vs 1.4%; P = .15) and (4.1% vs 5.4%, P = .39), respectively. There were no cases of toxic megacolon during the study period. Conclusions: The change to an algorithm-based C. difficile testing method had a significant impact on the clinicians’ decisions to treat patients with a positive test, as most patients with a GDH+/Tox−/PCR+ result did not receive treatment. These patients did not suffer more adverse outcomes compared to those who were treated, which has implications for testing practices. It remains to be explored whether clinicians are using clinical criteria to decide whether or not to treat patients with a positive algorithm-based test, as opposed to the more reflexive treatment of patients with a positive PCR test.Funding: NoneDisclosures: None

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