LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study

IntroductionGrades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsiesMethods and analysisThis study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library preparation and targeted capture will be performed using the TruSight Tumor 170 (TST170) kit and samples sequenced on NextSeq 550 (Illumina) using NextSeq V.2.5 hi output reagents, according to the manufacturer’s instructions. Data analysis will be performed using the Illumina BaseSpace TST170 app v1.02 and a custom tertiary pipeline, implemented within the Clinical Genomics Workspace software platform from PierianDx (also refer to section 3.2). Primary outcomes for the study will be the number of patients enrolled and the number of patients who complete molecular screening. Secondary outcomes will include the proportion of screened patients enrolled; proportion of patients who complete molecular screening; the turn-around time of molecular screening; and the value of a brain tumour specific multi-disciplinary tumour board, called the molecular tumour advisory panel as measured by the proportion of patients in whom the treatment recommendation was refined compared with the recommendations from the automated bioinformatics platform of the reference laboratory testing.Ethics and disseminationThe study was approved by the lead Human Research Ethics Committee of the Sydney Local Health District: Protocol No. X19-0383. The study will be conducted in accordance with the principles of the Declaration of Helsinki 2013, guidelines for Good Clinical Practice and the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2007, updated 2018 and as amended periodically). Results will be disseminated using a range of media channels including newsletters, social media, scientific conferences and peer-reviewed publications.Trial registration numberACTRN12620000087954; Pre-results.

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Large outbreak of viral gastroenteritis caused by contaminated drinking water in Apulia, Italy, May - October 2006

Weekly releases (1997–2007) ◽

10.2807/esw.12.16.03176-en ◽

2007 ◽

Vol 12 (16) ◽

Cited By ~ 2

Author(s):

D Martinelli ◽

R Prato ◽

M Chironna ◽

A Sallustio ◽

G Caputi ◽

...

Keyword(s):

Acute Diarrhoea ◽

Field Investigation ◽

Reference Laboratory ◽

Local Health ◽

Viral Gastroenteritis ◽

Local Health Unit ◽

Accident And Emergency ◽

Number Of Patients ◽

Large Outbreak ◽

Contaminated Drinking Water

At the end of July 2006, an unusually high number of patients with acute diarrhoea were reported by the accident and emergency departments in Taranto, Apulia. Subsequently, a field investigation was conducted jointly by the Apulia Regional Epidemiological Observatory and the Regional Reference Laboratory in Bari, and the Epidemiological Department of Taranto Local Health Unit.

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Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

Current Drug Safety ◽

10.2174/1574886313666181001120752 ◽

2019 ◽

Vol 14 (1) ◽

pp. 31-36

Author(s):

Raafat Abdel-Malek ◽

Kyrillus S. Shohdy ◽

Noha Abbas ◽

Mohamed Ismail ◽

Emad Hamada ◽

...

Keyword(s):

Pilot Study ◽

Adverse Events ◽

Urothelial Carcinoma ◽

Transitional Cell ◽

Chemotherapeutic Agents ◽

Serious Adverse Events ◽

Platinum Based Chemotherapy ◽

Number Of Patients ◽

Advanced Urothelial Carcinoma ◽

Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

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A Collaborative Deprescribing Intervention in a Subacute Medical Outpatient Clinic: A Pilot Randomized Controlled Trial

Metabolites ◽

10.3390/metabo11040204 ◽

2021 ◽

Vol 11 (4) ◽

pp. 204

Author(s):

Anissa Aharaz ◽

Jens Henning Rasmussen ◽

Helle Bach Ølgaard McNulty ◽

Arne Cyron ◽

Pia Keinicke Fabricius ◽

...

Keyword(s):

Pilot Study ◽

Controlled Trial ◽

Inappropriate Medication ◽

Intervention Group ◽

Control Group ◽

Randomized Controlled ◽

Patient Interviews ◽

Number Of Patients ◽

Multimorbid Patients ◽

And Control

Medication deprescribing is essential to prevent inappropriate medication use in multimorbid patients. However, experience of deprescribing in Danish Subacute Medical Outpatient Clinics (SMOCs) is limited. The objective of our pilot study was to evaluate the feasibility and sustainability of a collaborative deprescribing intervention by a pharmacist and a physician to multimorbid patients in a SMOC. A randomized controlled pilot study was conducted, with phone follow-up at 30 and 365+ days. A senior pharmacist performed a systematic deprescribing intervention using the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, the Danish deprescribing list, and patient interviews. A senior physician received the proposed recommendations and decided which should be implemented. The main outcome was the number of patients having ≥1 medication where deprescribing status was sustained 30 days after inclusion. Out of 76 eligible patients, 72 (95%) were included and 67 (93%) completed the study (57% male; mean age 73 years; mean number of 10 prescribed medications). Nineteen patients (56%) in the intervention group and four (12%) in the control group had ≥1 medication where deprescribing status was sustained 30 days after inclusion (p = 0.015). In total, 37 medications were deprescribed in the intervention group and five in the control group. At 365+ days after inclusion, 97% and 100% of the deprescribed medications were sustained in the intervention and control groups, respectively. The three most frequently deprescribed medication groups were analgesics, cardiovascular, and gastrointestinal medications. In conclusion, a collaborative deprescribing intervention for multimorbid patients was feasible and resulted in sustainable deprescribing of medication in a SMOC.

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Diagnostic imaging of the larynx: autofluorescence of laryngeal tumours using the helium-cadmium laser

The Journal of Laryngology & Otology ◽

10.1017/s002221510012941x ◽

1995 ◽

Vol 109 (2) ◽

pp. 108-110 ◽

Cited By ~ 70

Author(s):

Meredydd Lloyd Harries ◽

Stephen Lam ◽

Calum MacAulay ◽

Jianan Qu ◽

Branko Palcic

Keyword(s):

Pilot Study ◽

Diagnostic Imaging ◽

Vocal Folds ◽

Tumour Tissue ◽

Laryngeal Tumours ◽

Bronchial Tissue ◽

Fluorescence Images ◽

Detection And Localization

AbstractThe use of tissue autofluorescence for the detection and localization of cancer of the larynx is described. In this pilot study, eight patients with probable carcinoma of the vocal folds underwent laryngoscopy in which the tissue autofluorescence spectra of normal and pathologically confirmed tumour tissue were acquiredin vivo. Fluorescence images of the suspect areas were also acquired using the LIFE system (Xillix Technologies Corp.). The results suggest that the autofluorescence properties of laryngeal tissue, under 442 nm illumination, are similar to those of bronchial tissue and that the LIFE system has the potential to increase the accuracy of staging of cancer of the larynx and also to allow earlier diagnosis of tumours and theirrecurrence

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Pilot Study on Frailty and Functionality on Routine Clinical Assessment in Allogeneichematopoietic Cell Transplantation to Predict Outcomes

Blood ◽

10.1182/blood-2019-126071 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 380-380 ◽

Cited By ~ 1

Author(s):

Maria Queralt Salas ◽

Eshetu G Atenafu ◽

Ora Bascom ◽

Leeann Wilson ◽

Arjun Law ◽

...

Keyword(s):

Stem Cell ◽

Pilot Study ◽

Stem Cell Transplantation ◽

Grip Strength ◽

Cell Transplantation ◽

Waiting Time ◽

Acute Gvhd ◽

Number Of Patients ◽

And Function

Introduction: Frailty can adversely affect the outcomes of allogeneic hematopoietic stem cell transplantation (alloHSCT) but is difficult to measure in busy transplant clinics. The limited published studies have used dedicated trained persons and comprehensive geriatric assessment (GA) tools, which are time consuming (Muffly LS, Haematologica 2014; Holmes HM, J Geriatr Oncol 2014; Rodrigues M, J Geriatr Oncol 2019). The difficulty in application of GA tools by transplant clinicians, residents and nurses in their clinics has resulted in low adoption rates in routine practice. At our center we adopted selected tests for frailty and function which could be conducted during pre-transplant consultation in a busy clinic, without extra waiting time for patients, and using existing staff. The Timed up and Go test (TUGT) was adopted as it could be done in any closed clinic room, without need for a corridor. Thus it was considered safer than a gait speed test and was even applicable to patients in "isolation". We aim to share a preliminary analysis of the applicability and correlation between our selected frailty assessment with transplant outcomes and complications. Methods: Patients referred for transplant underwent the following assessments conducted by different providers. All ages were included. Relevant tests and source of data are as follows: Frailty and function by clinician evaluating (a) Clinical Frailty scale (CFS) with 9 points based on clinical judgement (Rockwood 2005) (b) Lawton's Instrumental activities of daily living (IADL). Objective physical performance by nursing BMT coordinator using (a) TUGT and (b) Grip strength using hydraulic "Jamar" hand dynamometer conducted in clinic room at time of documentation. Self assessment by patient completing (a) Self-rated health (SRH) question and (b) a question on falls. Blood tests (a) CRP (b) Albumin. The present study is a single center prospective observational study. Patients who did not proceed to transplant were excluded. Ninety-six consecutive adult allo-HSCT patients were eligible for the present analysis, updated on July 2019. The parameters were individually correlated with overall survival (OS), non-relapse mortality (NRM), cumulative incidence (cum.Inc) of acute GVHD, median time of transplant hospitalization and readmissions. Multivariate analysis was not performed in this pilot study due to limited number of patients and low frequency of adverse events. Results: Baseline characteristics and main post-transplant information are noted in Table 1. Median follow up of cohort was 5 months. Table 2 shows the main outcomes (with normal values). For the entire cohort the median OS at 6 months was 73.9% (range 61.7-82.8), NRM at day+100 was 8.7% (range 2.6-14.7), Cum.Inc of Acute GVHD 41.1% (range 30.1-52.1), Cum.Inc gr II-IV acute GVHD was 25.7% (range 15.6-35.9). Relapse occurred in 8 cases (8.3%) and deaths in 23 (23.9%). A TUGT of more than 10 seconds and raised CRP predicted poor OS (p<0.05). Abnormal TUGT, SRH question score of <A (excellent), lower albumin levels and raised CRP levels correlated with high NRM (p<0.05). A Clinical Frailty Score of more than 2, limitations of 1 or more IADLs, Grip strength below normal for age and sex, TUGT >10 seconds, SRH question <A, and lower albumin level were significant predictors for a longer median duration of transplant hospitalization. No frailty or functionality parameter correlated significantly with the Cum.Inc of any grade of acute GVHD, grade II-IV acute GVHD or the risk of rehospitalization after alloHSCT. Conclusions: Our pilot study shows that with selected brief tools, frailty and functionality can be assessed as part of routine clinical practice in allogeneic-stem cell transplantation in all age groups without extra waiting time for patients or additional human resources. TUGT is a useful prognostic tool which can be conducted in a clinic room and correlates with OS, NRM, and duration of hospitalization. Larger number of patients and longer follow-up will help to evaluate the different assessment modalities as prognostic tools in allo-HSCT and their wider applicability. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Gilead: Honoraria; Celgene: Honoraria; Therakos: Honoraria.

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CAPD Fluid Examination using the Bactec 460

Peritoneal Dialysis International ◽

10.1177/089686088600600104 ◽

1986 ◽

Vol 6 (1) ◽

pp. 9-11 ◽

Cited By ~ 5

Author(s):

Maurice Terence Dalton ◽

Eva Prevost

Keyword(s):

Pilot Study ◽

Blood Culture ◽

Culture System ◽

Work Load ◽

Major Advance ◽

Blood Culture System ◽

Fluid Analysis ◽

Number Of Patients ◽

Daily Sampling ◽

Stage Renal Disease

In the microbiological laboratory CAPD fluid analysis is an unstandardized and sometimes a labor intensive procedure. This pilot study was set up to demonstrate the value of in-place technology -the Bactec 460 blood culture system, in reducing the work-load. Our results indicate that it is at least as effective as other, more tedious conventional methods. Since its introduction, continuous ambulatory peritoneal dialysis (CAPD) has proved to be a major advance in the management of end-stage renal disease (I). Despite refinements in technique over the years leading to more widespread use of CAPD, the major hazard remains peritonitis and other infections (2). Also peritonitis is a major cause of failure of CAPD (3,4). Because CAPD allows more freedom of movement, several laboratories receive the postdialysis effluents from the same patient; furthermore there is no widely recognized, single method for the examination of these fluids (2, 5). Some centers recommend daily sampling for microbiological studies and while this is ideal for patient management, it imposes a significant workload on the microbiology laboratory, particularly in a larger centre (2). Currently it appears that the number of patients on CAPD will continue to increase for the foreseeable future and so will the numbers of specimens to be examined. To facilitate these examinations, we carried out a five-month pilot study using the Bactec 460 blood-culture system to examine CAPD fluids. We compared these results with a conventional method used previously in our laboratory.

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Intensive diagnostic management of coronavirus disease 2019 (COVID-19) in academic settings in Japan: challenge and future

Inflammation and Regeneration ◽

10.1186/s41232-020-00147-2 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Tokio Hoshina ◽

Hiroka Aonuma ◽

Manabu Ote ◽

Tatsuya Sakurai ◽

Erisha Saiki ◽

...

Keyword(s):

Diagnostic Testing ◽

Basic Research ◽

Diagnostic Value ◽

Turnaround Time ◽

Patient Treatment ◽

Emerging Infections ◽

University Hospitals ◽

Number Of Patients ◽

Academic Settings ◽

The Impact

Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in Wuhan, China, and has spread globally to most countries. In Japan, the first COVID-19 patient was identified on January 15, 2020. By June 30, the total number of patients diagnosed with COVID-19 reached 18,000. The impact of molecular detection of pathogens is significant in acute-care settings where rapid and accurate diagnostic measures are critical for decisions in patient treatment and outcomes of infectious diseases. Polymerase chain reaction (PCR)-based methods, such as quantitative PCR (qPCR), are the most established gene amplification tools and have a comprehensive range of clinical applications, including detecting a variety of pathogens, even novel agents causing emerging infections. Because SARS-CoV-2 contains a single-stranded RNA genome, reverse-transcription qPCR (RT-qPCR) has been broadly employed for rapid and sensitive quantitative measurements of viral RNA copy numbers. The RT-qPCR method, however, still requires time-consuming reactions with two different enzymes in addition to isolation of RNA from patient samples, limiting the numbers of testing institutions for diagnosing SARS-CoV-2 infection. Japan is known to have performed a relatively small number of PCR tests as well as confirmed cases among developed nations; as of June 30, 2020, approximately 390,000 people in Japan had undergone PCR tests. Given the devastating impact on medical services and the scale of demand for diagnostic testing of COVID-19, it has been proposed that academic settings such as basic research departments in university/college can be engaged in diagnosing, especially in university hospitals or academic medical centers. In collaboration with established diagnostic laboratories, academic facilities can divert their function to detecting virus from patients with suspected COVID-19, adopting existing specialized expertise in virus handling, molecular work, and data analysis. This in-house testing strategy facilitates the rapid diagnosing of thousands of samples per day and reduces sample turnaround time from 1 week to less than 24 h. This review provides an overview of the general principles, diagnostic value, and limitations of COVID-19 diagnosis platforms in Japan, in particular in-house testing at academic settings.

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Management evaluation of metastasis in the brain (MEMBRAIN)—a United Kingdom and Ireland prospective, multicenter observational study

Neuro-Oncology Practice ◽

10.1093/nop/npz063 ◽

2019 ◽

Vol 7 (3) ◽

pp. 344-355

Author(s):

Josephine Jung ◽

Jignesh Tailor ◽

Emma Dalton ◽

Laurence J Glancz ◽

Joy Roach ◽

...

Keyword(s):

Decision Making ◽

United Kingdom ◽

Significant Proportion ◽

Whole Brain Radiotherapy ◽

Disease Status ◽

Treatment Recommendation ◽

Multicenter Cohort Study ◽

Multicenter Observational Study ◽

Primary Disease ◽

Number Of Patients

Abstract Background In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making. Methods A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database. Results A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases. Conclusions This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.

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Description of the effect of patient flow, junior doctor supervision and pandemic preparation on the ability of emergency physicians to provide direct patient care

Australian Health Review ◽

10.1071/ah20180 ◽

2020 ◽

Vol 44 (5) ◽

pp. 741

Author(s):

Andy Lim ◽

Namankit Gupta ◽

Alvin Lim ◽

Wei Hong ◽

Katie Walker

Keyword(s):

Pilot Study ◽

Patient Care ◽

Patient Flow ◽

High Volume ◽

Direct Patient Care ◽

Published Data ◽

Emergency Physicians ◽

Cross Sectional ◽

Number Of Patients ◽

Process Factors

ObjectiveA pilot study to: (1) describe the ability of emergency physicians to provide primary consults at an Australian, major metropolitan, adult emergency department (ED) during the COVID-19 pandemic when compared with historical performance; and (2) to identify the effect of system and process factors on productivity. MethodsA retrospective cross-sectional description of shifts worked between 1 and 29 February 2020, while physicians were carrying out their usual supervision, flow and problem-solving duties, as well as undertaking additional COVID-19 preparation, was documented. Effect of supervisory load, years of Australian registration and departmental flow factors were evaluated. Descriptive statistical methods were used and regression analyses were performed. ResultsA total of 188 shifts were analysed. Productivity was 4.07 patients per 9.5-h shift (95% CI 3.56–4.58) or 0.43 patients per h, representing a 48.5% reduction from previously published data (P<0.0001). Working in a shift outside of the resuscitation area or working a day shift was associated with a reduction in individual patient load. There was a 2.2% (95% CI: 1.1–3.4, P<0.001) decrease in productivity with each year after obtaining Australian medical registration. There was a 10.6% (95% CI: 5.4–15.6, P<0.001) decrease in productivity for each junior physician supervised. Bed access had no statistically significant effect on productivity. ConclusionsEmergency physicians undertake multiple duties. Their ability to manage their own patients varies depending on multiple ED operational factors, particularly their supervisory load. COVID-19 preparations reduced their ability to see their own patients by half. What is known about the topic?An understanding of emergency physician productivity is essential in planning clinical operations. Medical productivity, however, is challenging to define, and is controversial to measure. Although baseline data exist, few studies examine the effect of patient flow and supervision requirements on the emergency physician’s ability to perform primary consults. No studies describe these metrics during COVID-19. What does this paper add?This pilot study provides a novel cross-sectional description of the effect of COVID-19 preparations on the ability of emergency physicians to provide direct patient care. It also examines the effect of selected system and process factors in a physician’s ability to complete primary consults. What are the implications for practitioners?When managing an emergency medical workforce, the contribution of emergency physicians to the number of patients requiring consults should take into account the high volume of alternative duties required. Increasing alternative duties can decrease primary provider tasks that can be completed. COVID-19 pandemic preparation has significantly reduced the ability of emergency physicians to manage their own patients.

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