‘I actually felt like I was a researcher myself.’ On involving children in the analysis of qualitative paediatric research in the Netherlands

ObjectivesTo evaluate the feasibility of a new approach to paediatric research whereby we involved children in analysing qualitative data, and to reflect on the involvement process.SettingThis was a single-centre, qualitative study in the Netherlands. It consisted of research meetings with individual children at home (Phase I) or group meetings at school (Phase II). In Phase I, we identified themes from a video interview during five one-on-one meetings between a child co-researcher and the adult researcher. In Phase II, during two group meetings, we explored the themes in detail using fragments from 16 interviews.ParticipantsWe involved 14 school children (aged 10 to 14 years) as co-researchers to analyse children’s interviews about their experience while participating in medical research. Notes were taken, and children provided feedback. A thematic analysis was performed using a framework approach.ResultsAll co-researchers identified themes. The time needed to complete the task varied, as did the extent to which the meetings needed to be structured to improve concentration. The children rated time investment as adequate and they considered acting as co-researcher interesting and fun, adding that they had learnt new skills and gained new knowledge. The experience also led them to reflect on health matters in their own lives. The adult researchers considered the process relatively time intensive, but the project did result in a more critical assessment of their own work.ConclusionThe new, two-phase approach of involving children to help analyse qualitative data is a feasible research method. The novelty lies in involving children to help identify themes from original interview data, thereby limiting preselection of data by adults, before exploring these themes in detail. Videos make it easier for children to understand the data and to empathise with the interviewees, and limits time investment.

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Nurses’ educational needs when dealing with aggression from patients and their families: a mixed-methods study

BMJ Open ◽

10.1136/bmjopen-2020-041711 ◽

2021 ◽

Vol 11 (1) ◽

pp. e041711

Author(s):

Kana Sato ◽

Yoshimi Kodama

Keyword(s):

Mixed Methods ◽

Nursing Students ◽

Phase I ◽

Phase Ii ◽

Mixed Methods Study ◽

Self Awareness ◽

Two Phase ◽

Sequential Mixed Methods ◽

Nursing Professionals ◽

Educational Contents

ObjectivesTo explore the type of education needed for nurses when dealing with aggression from patients and their families.DesignA two-phase sequential mixed-methods study.SettingThis study was conducted in Japan, with phase I from March to November 2016 and phase II in November 2018.Main outcome measuresThe challenges faced by nurses when dealing with incidents of aggression from the neutral perspective of neither nurse nor patient/family and perceptions of the educational contents developed in this study. Descriptive analyses were used to examine the data retrieved from both phases.ParticipantsPhase I entailed semistructured interviews among 11 neutral-party participants who observed aggressive incidents between nurses and patients/families. Phase II consisted of a web survey conducted among 102 nursing students and 308 nursing professionals.ResultsPhase I resulted in the identification of the following five main educational components: understanding the mechanisms of anger and aggression, maintaining self-awareness, observant listening, managing the self-impression, and communicating based on specific disease characteristics. Each component was related to improved communication through self-awareness. The results of phase II indicated that participants positively perceived these educational contents as likely to be effective for dealing with aggression from patients/families.ConclusionsThis study clarified the type of education needed for nurses when dealing with aggression based on multiple viewpoints. Specifically, neutral-party interviews revealed that communication should be improved through self-awareness. A subsequent survey among nurses and nursing students showed that the identified educational contents were positively received.

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Mixed methods study protocol to examine perceptions of family medicine among long-term patients of a family medicine clinic in Japan

BMJ Open ◽

10.1136/bmjopen-2020-037113 ◽

2020 ◽

Vol 10 (9) ◽

pp. e037113

Author(s):

Kotaro Sato ◽

Ryoko Michinobu ◽

Tesshu Kusaba

Keyword(s):

Primary Care ◽

Mixed Methods ◽

Family Medicine ◽

Phase I ◽

Phase Ii ◽

Medical Specialty ◽

Structured Interviews ◽

Two Phase ◽

Care Systems

IntroductionFamily physicians or general practitioners play central roles in many countries’ primary care systems, but family medicine (FM) remains relatively unestablished in Japan. Previous studies in Japan have examined the general population’s understanding of FM as a medical specialty, but none have explored this topic using actual FM clinic patients. Here, we describe a protocol to explore the perceptions of FM among long-term patients of one of Japan’s oldest FM clinics.Methods and analysisThe study will be conducted at the Motowanishi Family Clinic in Hokkaido, Japan, using patients who have attended the clinic for over 10 years. The analysis will adopt a two-phase explanatory sequential mixed methods design. During phase I, quantitative data from participants’ medical records will be collected and reviewed, and patients’ perceptions of FM will be assessed through a questionnaire. The correlations between participants’ knowledge that the clinic specialises in FM and various characteristics will be examined. In phase II, qualitative data will be collected through semi-structured interviews of approximately 10 participants selected using maximum variation sampling based on phase I results. A thematic analysis will be conducted in phase II to identify patients’ perceptions and changes in perceptions. Finally, each theme identified in phase II will be transformed into a quantitative variable to analyse the relationships between the phases. A joint display will be used to integrate the phases’ findings and examine how phase II results explain phase I results.Ethics and disseminationThe institutional review board of the Japan Primary Care Association has approved this research (2019-003). The results will be presented at the association’s annual academic meeting and submitted for publication in relevant journals. The findings will also be provided to the patients via the clinic’s internal newsletter.

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COVID-19 and radiation oncology: the experience of a two-phase plan within a single institution in central Italy

Radiation Oncology ◽

10.1186/s13014-020-01670-9 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Luciana Caravatta ◽

Consuelo Rosa ◽

Maria Bernadette Di Sciascio ◽

Andrea Tavella Scaringi ◽

Angelo Di Pilla ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Central Italy ◽

Significant Risk ◽

Tumor Board ◽

Radiotherapy Planning ◽

Two Phase ◽

Hospital Environments ◽

Two Phases

Abstract Background COVID-19 in Italy has led to the need to reorganize hospital protocols with a significant risk of interruption to cancer treatment programs. In this report, we will focus on a management model covering the two phases of the COVID-19 emergency, namely lockdown-phase I and post-lockdown-phase II. Methods The following steps were taken in the two phases: workload during visits and radiotherapy planning, use of dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, hospital environments and intra-institutional meetings and tumor board management. Due to the guidelines set out by the Ministry of Health, oncological follow-up visits were interrupted during the lockdown-phase I; consequently, we set about contacting patients by telephone, with laboratory and instrumental exams being viewed via telematics. During the post-lockdown-phase II, the oncological follow-up clinic reopened, with two shifts operating daily. Results By comparing our radiotherapy activity from March 9 to May 4 2019 with the same period in 2020 during full phase I of the COVID-19 emergency, similar results were achieved. First radiotherapy visits, Simulation Computed Tomography and Linear Accelerator treatments amounted to 123, 137 and 151 in 2019 compared with 121, 135 and 170 in 2020 respectively. There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals, who were all negative to the swab tests performed. Conclusion During both phases of the COVID-19 emergency, the planned model used in our own experience guaranteed both continuity in radiotherapy treatments whilst neither reducing workload nor interrupting treatment and, as such, it ensured the safety of cancer patients, hospital environments and staff.

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Combination of Oxaliplatin Plus Irinotecan in Patients With Gastrointestinal Tumors: Results of Two Independent Phase I Studies With Pharmacokinetics

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.6.1751 ◽

1999 ◽

Vol 17 (6) ◽

pp. 1751-1751 ◽

Cited By ~ 94

Author(s):

Ernesto Wasserman ◽

Caroline Cuvier ◽

François Lokiec ◽

François Goldwasser ◽

Salima Kalla ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Performance Status ◽

Maximum Tolerated Dose ◽

Two Phase ◽

Phase I Studies ◽

Phase Ii Studies ◽

Minute Period ◽

Grade 3 ◽

Febrile Episodes

PURPOSE: Two phase I studies of the oxaliplatin and irinotecan combination were performed in advanced gastrointestinal cancer patients to characterize the safety and pharmacokinetics of the regimen. PATIENTS AND METHODS: Patients with a performance status (PS) of ≤2 and normal hematologic, hepatic, and renal functions received oxaliplatin (2-hour intravenous infusion) followed 1 hour later by irinotecan administered over a 30-minute period, every 3 weeks. Dose levels that were explored ranged from 85 to 110 mg/m2 for oxaliplatin and 150 to 250 mg/m2 for irinotecan. Plasma pharmacokinetics of total and ultrafiltrable platinum, irinotecan, SN-38, and its glucuronide, SN-38G, were determined. RESULTS: Thirty-nine patients with gastrointestinal carcinomas (24 with colorectal cancer [CRC], four with pancreas cancer, four with gastric cancer, three with hepatocarcinoma, and four with other) received 216 treatment cycles. Median age was 54 years (range, 21 to 72 years); 95% had PS of 0 to 1; all but six had failed fluorouracil (5-FU) chemotherapy. The maximum-tolerated dose was oxaliplatin 110 mg/m2 plus irinotecan 200 mg/m2 in one study and oxaliplatin 110 mg/m2 plus irinotecan 250 mg/m2 in the other study. Grade 3 to 4 diarrhea and febrile neutropenia were dose-limiting toxicities; other toxicities included emesis and dose-cumulative neuropathy. Recommended dose for phase II studies is oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2. At this dose (12 patients, 65 cycles), grade 3 and 4 toxicities per patient included the following: emesis in 42% of patients, neutropenia in 33% (febrile episodes in 17%), peripheral neuropathy in 25%, delayed diarrhea in 17%, and thrombocytopenia in 8%. Two patients with Gilbert's syndrome experienced severe irinotecan toxicity. No plasmatic pharmacokinetic interactions were detected. Seven partial responses were observed in 24 CRC patients. CONCLUSION: This combination is feasible, with activity in 5-FU–resistant CRC patients. Phase I studies that explore the every-2-weeks schedule, in addition to phase II studies of this schedule (as well as in combination with 5-FU) as second-line therapy of metastatic CRC, are ongoing.

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Augmented pseudo-likelihood estimation for two-phase studies

Statistical Methods in Medical Research ◽

10.1177/0962280219833415 ◽

2019 ◽

Vol 29 (2) ◽

pp. 344-358

Author(s):

Claudia Rivera-Rodriguez ◽

Sebastien Haneuse ◽

Molin Wang ◽

Donna Spiegelman

Keyword(s):

Phase I ◽

Phase Ii ◽

Likelihood Estimation ◽

Weighted Likelihood ◽

Finite Sample ◽

Cross Sectional Survey ◽

Two Phase ◽

Cross Sectional ◽

Pseudo Likelihood ◽

Pseudo Likelihood Estimation

In many public health and medical research settings, information on key covariates may not be readily available or too expensive to gather for all individuals in the study. In such settings, the two-phase design provides a way forward by first stratifying an initial (large) phase I sample on the basis of covariates readily available (including, possibly, the outcome), and sub-sampling participants at phase II to collect the expensive measure(s). When the outcome of interest is binary, several methods have been proposed for estimation and inference for the parameters of a logistic regression model, including weighted likelihood, pseudo-likelihood and maximum likelihood. Although these methods yield consistent estimation and valid inference, they do so solely on the basis of the phase I stratification and the detailed covariate information obtained at phase II. Moreover, they ignore any additional information that is readily available at phase I but was not used as part of the stratified sampling design. Motivated by the potential for efficiency gains, especially concerning parameters corresponding to the additional phase I covariates, we propose a novel augmented pseudo-likelihood estimator for two-phase studies that makes use of all available information. In contrast to recently-proposed weighted likelihood-based methods that calibrate to the influence function of the model of interest, the methods we propose do not require the development of additional models and, therefore, enjoy a degree of robustness. In addition, we expand the broader framework for pseudo-likelihood based estimation and inference to permit link functions for binary regression other than the logit link. Comprehensive simulations, based on a one-time cross sectional survey of 82,887 patients undergoing anti-retroviral therapy in Malawi between 2005 and 2007, illustrate finite sample properties of the proposed methods and compare their performance competing approaches. The proposed method yields the lowest standard errors when the model is correctly specified. Finally, the methods are applied to a large implementation science project examining the effect of an enhanced community health worker program to improve adherence to WHO guidelines for at least four antenatal visits, in Dar es Salaam, Tanzania.

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Novel organic arsenic molecule darinaparsin: Development of IV and oral forms

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8501 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8501-8501 ◽

Cited By ~ 2

Author(s):

I. Lossos ◽

M. D. Craig ◽

M. S. Tallman ◽

R. V. Boccia ◽

P. R. Conkling ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Phase Ii Study ◽

Complete Response ◽

Median Number ◽

Two Phase ◽

Phase I Studies ◽

Advanced Malignancies

8501 Background: Darinaparsin (ZIO-101) is a novel organic arsenical active against diverse cancers in vitro, and in vivo. Darinaparsin i.v. activity in lymphoma is being evaluated in a phase II study. Darinaparsin is orally bioavailable; the oral form is being investigated in two phase I studies in patients with advanced malignancies. Methods: Phase II trial is being conducted in patients diagnosed with advanced lymphomas who had ≥ 1 prior therapy. Patients receive 300 mg/m2/day of darinaparsin i.v. for 5 consecutive days every 28 days. Efficacy and safety are evaluated by standard criteria. Phase I oral dose escalation studies are being conducted in patients with advanced malignancies and explore safety, MTD, DLTs and preliminary efficacy of continuous and intermittent dosing schedules. Starting continuous dose is 100 mg BID for 3 weeks with 1 week rest, starting intermittent dose is 300 mg twice weekly for 3 weeks followed by 1 week rest. Results: The phase II study has accrued 28 lymphoma patients (21 non-Hodgkin's, 7 Hodgkin's); median age at baseline 61 years, ECOG ≤2, median number of prior therapies 3. Seventeen subjects have received at least 2 cycles of darinaparsin and are evaluable for efficacy. Of these, 1 subject (PTCL) has achieved a complete response, 3 - partial responses (2 marginal zone, 1 Hodgkin's), and 4 stable disease (2 PTCL, 1 DLBCL, 1 Hodgkin's). A total of 63 cycles of darinaparsin have been administered to subjects with lymphoma. No Gr. 3 or higher drug-related AEs were reported. Two SAEs were considered possibly drug-related (fall; neutropenic fever). Phase I studies accrued 35 patients; median age at baseline 58 years, ECOG ≤2, median number of prior therapies 3. Predominant tumor types include: colorectal (17), pancreatic (3), NHL (3). Current darinaparsin dose levels: continuous 200 mg BID, 2× weekly 900 mg. Of 18 patients evaluable for efficacy, 10 demonstrate SD ≥ 3 cycles. Oral darinaparsin bioavailability is 58%. Drug-related AEs include nausea/vomiting, fatigue, decreased appetite/anorexia. Conclusions: Darinaparsin is active in heavily pretreated patients with advanced lymphoma and has been very well tolerated. Oral darinaparsin is also well tolerated, and shows early activity. [Table: see text]

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A globally convergent tracking controller for the X4 flyer rotor craft for reference trajectories with positive thrust

Robotica ◽

10.1017/s0263574704000165 ◽

2004 ◽

Vol 22 (4) ◽

pp. 375-388 ◽

Cited By ~ 5

Author(s):

Brian J. Driessen ◽

Alexandre L. Robin

Keyword(s):

Phase I ◽

Phase Ii ◽

Tracking Error ◽

Reference Trajectory ◽

Two Phase ◽

Globally Convergent ◽

Tracking Controller ◽

Control Objective ◽

Yaw Angle ◽

Angle Tracking

In this paper we present a globally convergent and ultimately exponentially convergent tracking controller for an X4 Flyer rotor craft. The desired or reference trajectory is restricted in one way: its scalar thrust must be uni signed and bounded away from zero. The proposed controller is a two phase one. Phase I converges the attitude (orientation) error and thrust error to zero globally and ultimately exponentially. Phase II is a position tracking and relative yaw angle tracking controller, which is not globally convergent by itself. By carefully postponing a switch from Phase I to Phase II, we are able to assure that Phase II will ultimately drive the position error and relative yaw angle error to zero exponentially. In problem-statement/theorem/proof format, we define the system, the control objective, the proposed controller, and a rigorous proof that the controller maintains boundedness of all closed loop signals and provides global convergence of the tracking error to zero and also ultimately exponential convergence of the tracking error to zero.

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Adaptation of the DEMQOL-Proxy for routine use in care homes: a cross-sectional study of the reliability and validity of DEMQOL-CH

BMJ Open ◽

10.1136/bmjopen-2018-028045 ◽

2019 ◽

Vol 9 (8) ◽

pp. e028045 ◽

Cited By ~ 1

Author(s):

Laura J Hughes ◽

Nicolas Farina ◽

Thomas E Page ◽

Naji Tabet ◽

Sube Banerjee

Keyword(s):

Phase I ◽

Psychometric Properties ◽

Phase Ii ◽

Reliability And Validity ◽

Cross Sectional Study ◽

Care Staff ◽

Care Homes ◽

Two Phase ◽

Cross Sectional ◽

And Performance

ObjectiveTo investigate the routine use of a measure of quality of life (QoL) in care homes and assess its psychometric properties when used by care staff.DesignA cross-sectional two-phase study.Setting and participantsData were collected from care staff in seven care homes in East Sussex, England.MethodPhase I: The ability of care staff from two care homes to use the DEMQOL-Proxy without interviewer administration was assessed using agreement analysis between a self-administered and interviewer-administered version of the instrument. Based on these findings, DEMQOL-Proxy was adapted into a new version, DEMQOL-CH, for use as a self-administered instrument in care homes. We assessed agreement between the new DEMQOL-CH and DEMQOL-Proxy to ensure DEMQOL-CH was used correctly. Phase II: A preliminary assessment of the psychometric properties of DEMQOL-CH when used routinely was completed in a further five care homes.ResultsPhase I: Nineteen care staff from two care homes completed QoL measurements for residents. Systematic error was identified when staff self-completed the DEMQOL-Proxy without an interviewer. We modified the DEMOoL-Proxy to create DEMQOL-CH; this reduced the error, producing a version that could be used more accurately by care staff. Phase II: Eleven care staff from five care homes rated resident QoL routinely. DEMQOL-CH showed acceptable psychometric properties with satisfactory reliability and validity and a clear factor structure.ConclusionsThe research presents positive preliminary data on the acceptability, feasibility and performance of routine QoL measurement in care homes using an adapted version of DEMQOL-Proxy, the DEMQOL-CH. Results provide evidence to support the concept that routine measurement of QoL may be possible in care homes. Research is needed to refine and test the methodology and instrument further and to explore the potential for benefits to residents, staff and care homes in larger and more representative populations.

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Biomodulation of capecitabine by weekly paclitaxel and carboplatin in patients with advanced solid tumor malignancies: A dose-escalating phase I study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2569 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2569-2569

Author(s):

M. B. Lustberg ◽

J. Nuovo ◽

J. P. Thomas ◽

P. J. Monk ◽

S. Kim ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Phase I Study ◽

Dihydropyrimidine Dehydrogenase ◽

Weekly Paclitaxel ◽

Unknown Primary ◽

Cancer Tissue ◽

Phase Ii Trials ◽

Two Phase ◽

Phase Ii Studies

2569 Background: A principal determinant of the therapeutic index with capecitabine-based treatment is the grade of thymidine phosphorylase (TP) activity in malignant tissue. The beneficial interactions of paclitaxel and carboplatin in upregulation of TP promise to make capecitabine more tumor specific and to provide the expected synergy. On the basis of the time-dependency and transiency for this upregulation we performed a phase I study of capecitabine in combination with weekly paclitaxel and carboplatin (CTX). Methods: Patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8–21, every 4 weeks. There were 5 planned dose levels (DL 1–5). Paclitaxel was escalated from 60 mg/m2 to 80 mg/m2 (DL 4) then 100 mg/m2 (DL 5). Capecitabine from 500 mg/m2 bid to 750 mg/2 bid (DL 2) then 1000 mg/m2 bid (DL 3–5). Carboplatin dose was fixed at AUC 6. Paraffin-embedded tissue was evaluated for expression of TP, thymidylate synthase and dihydropyrimidine dehydrogenase by immunohistochemistry. Results: 32 patients from Ohio State University (OSU) were enrolled. 84% had prior therapy. The most common grade 3/4 toxicities were neutropenia (59%), leukopenia (56%), and fatigue (16%). DLTs included neutropenic fever (1), prolonged neutropenia or thrombocytopenia (2) and diarrhea (1). The MTD was at DL 2. There were 10 confirmed responses [4 CR (esophagus, stomach, unknown primary and ampullary); 6 PRs (Pancreas (3), unknown primary, anal and esophagus] and stabilization of disease > 3 months in 12 patients. In normal tissue, there was no difference in expression levels of both TS and TP. On the other hand, in cancer tissue, TP levels seem to correlate with response whereas TS did not. Conclusions: CTX demonstrates acceptable tolerability. The recommended doses for phase II studies are capecitabine 750 mg/m2 bid, paclitaxel 60 mg/m2/week and carboplatin AUC=6. The acceptable toxicity profile in this dose schedule, and the promising antitumor activity observed warrant further evaluation of this regimen. Two phase II trials are already underway at OSU using this regimen for patients with pancreatic cancer and adenocarcinomas of unknown primary, the latter already actively enrolling patients. Pretreatment tumoral TP levels may help predict patients that are more likely to respond to CTX. Correlation of IHC data with responses will be presented at the meeting. [Table: see text]

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High-pressure neutron diffraction study of L-serine-I and L-serine-II, and the structure of L-serine-III at 8.1 GPa

Acta Crystallographica Section B Structural Science ◽

10.1107/s010876810601799x ◽

2006 ◽

Vol 62 (5) ◽

pp. 815-825 ◽

Cited By ~ 67

Author(s):

Stephen A. Moggach ◽

William G. Marshall ◽

Simon Parsons

Keyword(s):

Hydrogen Bonds ◽

Phase I ◽

Phase Ii ◽

Neutron Diffraction Study ◽

Neutron Powder Diffraction ◽

Hirshfeld Surface ◽

Phase Iii ◽

Two Phase ◽

Carboxylate Groups ◽

The Cost

The hydrostatic compression of L-serine-d 7 has been studied to 8.1 GPa by neutron powder diffraction. Over the course of this pressure range the compound undergoes two phase transitions, the first between 4.6 and 5.2 GPa, yielding L-serine-II, and the second between 7.3 and 8.1 GPa, yielding L-serine-III. All three polymorphs are orthorhombic, P212121, and feature chains of serine molecules connected via head-to-tail ND...O hydrogen bonds formed between ammonium and carboxylate groups. The chains are linked into a ribbon by a second set of ND...O hydrogen bonds. The hydroxyl moieties are distributed along the outer edges of the ribbon and in phase I they connect the ribbons into a layer by chains of OD...OD hydrogen bonds. The layers are connected together by a third set of ND...O hydrogen bonds, forming R^3_4(14) rings with substantial voids at their centres. In the transition from phase I to II these voids begin to close up, but at the cost of breaking the OD...OD chains. The OD...OD hydrogen bonds are replaced by shorter OD...O hydrogen bonds to carboxylate groups. At 7.3 GPa the O...O distance in the OD...O hydrogen bonds measures only 2.516 (17) Å, which is short, and we propose that the phase transition to phase III that occurs between 7.3 and 8.1 GPa relieves the strain that has built up in this region of the structure. The hydroxyl D atom now bifurcates between the OD...O contact that had been present in phase II and a new OD...O contact formed to a carboxylate in another layer. Hirshfeld surface fingerprint plots show that D...D interactions become more numerous, while hydrogen bonds actually begin to lengthen in the transition from phase II to III.

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