Abstract A92: Murine clinical trials program

A Novel Circulating Tumor Cell Assay for Non-Small Cell Lung Cancer Patients Undergoing Radiation Therapy

Sample size justification is an important consideration when planning a clinical trial, not only for the main trial but also for any preliminary pilot trial. When the outcome is a continuous variable, the sample size calculation requires an accurate estimate of the standard deviation of the outcome measure. A pilot trial can be used to get an estimate of the standard deviation, which could then be used to anticipate what may be observed in the main trial. However, an important consideration is that pilot trials often estimate the standard deviation parameter imprecisely. This paper looks at how we can choose an external pilot trial sample size in order to minimise the sample size of the overall clinical trial programme, that is, the pilot and the main trial together. We produce a method of calculating the optimal solution to the required pilot trial sample size when the standardised effect size for the main trial is known. However, as it may not be possible to know the standardised effect size to be used prior to the pilot trial, approximate rules are also presented. For a main trial designed with 90% power and two-sided 5% significance, we recommend pilot trial sample sizes per treatment arm of 75, 25, 15 and 10 for standardised effect sizes that are extra small (≤0.1), small (0.2), medium (0.5) or large (0.8), respectively.

Consortium of Eosinophilic Gastrointestinal Disease Researchers: Advancing the Field of Eosinophilic GI Disorders Through Collaboration

Results of a Phase 3 Study of Elderly Patients with Newly Diagnosed AML Treated with Sapacitabine and Decitabine Administered in Alternating Cycles

The technical quality of the work performed in clinical microbiology laboratories is regularly monitored, by external and internal schemes. Among the factors which might affect quality, attitudes of the laboratory staff are rarely considered. In this study, three concepts recognised by occupational psychologists as being important in the work place, Job Satisfaction, Commitment and Climate, were measured among microbiology biomedical scientists (BMSs) in the United Kingdom A self-report questionnaire was developed through preliminary interviews and two pilot studies. The perceptions of Job Satisfaction, Commitment (to both Profession and Organisation) and Climate were measured using established models from the occupational psychology literature. Three scales were devised specifically during this study to assess an individual BMS's perceptions of the standard of their own performance, the attitudes of their colleagues towards their work and the quality within their laboratory. A fourth measure was developed which collated all the ways that technical quality in clinical microbiology laboratories is currently measured in the UK into one scale. A total of 2415 questionnaires were posted to BMSs employed in National Health Service, Public Health Laboratory Service, Privately funded and University laboratories between November 1998 and February 1999. By March 1999,931 replies had been received, a response rate of 39%. BMSs reported lower Job Satisfaction than Medical Laboratory Technologists (the equivalent profession) in the United States. The results supported Meyer and Allen's (1991) three-component model of commitment and showed that BMSs experienced Professional Commitment more strongly than Organisational Commitment. An eight dimension model of Climate was developed, for clinical microbiology staff, from Newman's (1977) Perceived Work Environment scale. BMSs' perceptions of Individual Climate were affected by a number of demographic factors, but the most important was the size of the laboratory. The optimal number of people in a clinical microbiology department for positive Individual Climate was found to be less than 30. Affective Commitment to the Profession was the component of Commitment which most strongly influenced technical quality, through its positive relationship with an individual BMS's performance at work. Through aggregation of Climate scores for selected laboratories, it was shown that Laboratory Climate correlated positively with technical quality. From BMSs' perceptions of their laboratory's quality, a scale to assess `A Climate for Laboratory Quality' was developed. There was a strong positive relationship between `A Climate for Laboratory Quality' and a department's score on the measure of technical quality. Interviews with staff in four clinical microbiology laboratories supported the questionnaire findings with respect to Laboratory Climate. Qualitative data collected from a representative group of users of each of the four microbiology services showed that users' main concern was rapid turnaround time for results. Comments also highlighted the need for more effective communication between laboratory staff their colleagues working directly with patients.

Add-on Psoralea corylifolia mother tincture external application to individualized homeopathic medicines in treatment of vitiligo: Open, randomized, pragmatic, pilot trial

Background: Liver transplantation is a curative method for end-stage liver diseases, small unresectable hepatocellular carcinoma and acute liver failure. The discovery of immunosuppressive drugs increases the survival rate of liver transplanted recipients by reducing the incidence of graft rejection. Several complications such as renal dysfunction and increase risk of malignancy result from life-long treatment of transplanted recipients with immunosuppressant. If recipients are over-immunosuppressed, the risk of infection might be increased. On the other hands, if recipients are under-immunosuppressed, the risk of rejection would be increased. It should be useful if a test or a bio-marker that could predict and differentiate infection and rejection in transplanted recipients. Therefore, patients could be treated before adverse conditions. Although therapeutic drug monitoring has been performed as a routine test, it is mainly targeted for minimizing drug toxicity but little help in predicting infection and rejection. A new assay named Cylex? Immuknow? assay is designed to measure global cell mediated immunity of immunosuppressed population, by quantifying the amount of ATP synthesis by CD4+ T cells in response to PHA stimulation. It is undergoing evaluation in assessing the immune status of patients in order to predict the risk of infection and rejection, and also other conditions. (1, 2) Objectives: In this pilot study, we would like to evaluate ImmuKnow for predicting the risk of infection and rejection in liver transplanted recipients in Hong Kong. Methods: Blood samples were collected from liver transplanted recipients at different time intervals. The immune cell response of these patients was measured by Immuknow assay. Patients with low immune response might have a high risk of infection, patients with high immune response might have a high risk of rejection, and patients with moderate immune response should be clinically stable. Results and conclusion: Twenty-six blood samples were collected from eight transplanted recipients. The average Immuknow assay value for the post-transplant samples was 304.6 ng/mL ATP which represented moderate immune cell response according to the interpretation table. (Table 3) This was reasonable as the subjects were all clinically stable by well-controlled immunosuppression. The result was consistent with other studies. (1, 3) However, the association between low immune cell response and infection, and the association between high immune cell response and graft rejection could not be investigated as both of these conditions were not found in this pilot study. A larger study including episodes of infection and rejection should be conducted in order to evaluate the value of Immuknow assay more completely.

ACOPP Chemotherapy for Frontline Treatment of Older Patients with Hodgkin Lymphoma - a Pilot Study

Pilot Study Of Erlotinib In Patients With Acute Myeloid Leukemia

Topotecan and Paclitaxel in Previously Treated Patients with Relapsed Small Cell Lung Cancer: Phase II Trial of the North Central Cancer Treatment Group

Randomized controlled trial assessing a traditional Chinese medicine remedy in the treatment of primary dysmenorrhea

Recent studies from this laboratory with (212)Pb-trastuzumab have shown the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using (212)Pb as an in vivo generator of (212)Bi. The objective of the studies presented here was improvement of the efficacy of alpha-particle radioimmunotherapy using a chemotherapeutic agent. In a series of experiments, a treatment regimen was systematically developed in which athymic mice bearing i.p. LS-174T xenografts were injected i.p. with gemcitabine at 50 mg/kg followed by (212)Pb radioimmunotherapy. In a pilot study, tumor-bearing mice were treated with gemcitabine and, 24 to 30 h later, with 5 or 10 muCi (212)Pb-trastuzumab. Improvement in median survival was observed at 5 microCi (212)Pb-trastuzumab in the absence (31 days) or presence (51 days) of gemcitabine: 45 and 70 days with 10 microCi versus 16 days for untreated mice (P < 0.001). Multiple doses of gemcitabine combined with a single (212)Pb radioimmunotherapy (10 microCi) administration was then evaluated. Mice received three doses of gemcitabine: one before (212)Pb-trastuzumab and two afterwards. Median survival of mice was 63 versus 54 days for those receiving a single gemcitabine dose before radioimmunotherapy (P < 0.001), specifically attributable to (212)Pb-trastuzumab (P = 0.01). Extending these findings, one versus two treatment cycles was compared. A cycle consisted of sequential treatment with gemcitabine, 10 microCi (212)Pb radioimmunotherapy, then one or two additional gemcitabine doses. In the first cycle, three doses of gemcitabine resulted in a median survival of 90 versus 21 days for the untreated mice. The greatest benefit was noted after cycle 2 in the mice receiving 10 microCi (212)Pb-trastuzumab and two doses of gemcitabine with a median survival of 196.5 days (P = 0.005). Pretreatment of tumor-bearing mice with two doses of gemcitabine before (212)Pb radioimmunotherapy was also assessed with gemcitabine injected 72 and 24 h before (212)Pb-trastuzumab. The median survival was 56 and 76 days with one and two doses of gemcitabine versus 49 days without gemcitabine. The effect may not be wholly specific to trastuzumab because (212)Pb-HuIgG with two doses of gemcitabine resulted in a median survival of 66 days (34 days without gemcitabine). Treatment regimens combining chemotherapeutics with high-LET targeted therapy may have tremendous potential in the management and care of cancer patients.

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received 2500 IU/m2/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

BackgroundDupuytren’s disease is a progressive, fibroproliferative disorder resulting in nodules and collagenous cords within the palmar fascia of the hand. Until recently, surgery was the only treatment option for patients...

Letter to the Editor: Distant surgical teaching during <scp>COVID</scp>‐19 ‐ A pilot study on final year medical students