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  1. Article ; Online: Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel retinoic acid receptor-β agonist for treatment of spinal cord injury, in male healthy participants.

    Goncalves, Maria B / Mant, Tim / Täubel, Jörg / Clarke, Earl / Hassanin, Hana / Bendel, Daryl / Fok, Henry / Posner, John / Holmes, Jane / Mander, Adrian P / Corcoran, Jonathan P T

    British journal of clinical pharmacology

    2023  Volume 89, Issue 12, Page(s) 3573–3583

    Abstract: Aims: KCL-286 is an orally available agonist that activates the retinoic acid receptor (RAR) β2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). ...

    Abstract Aims: KCL-286 is an orally available agonist that activates the retinoic acid receptor (RAR) β2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). This adaptive dose escalation study evaluated the tolerability, safety and pharmacokinetics and pharmacodynamic activity of KCL-286 in male healthy volunteers to establish dosing to be used in the SCI patient population.
    Methods: The design was a double blind, randomized, placebo-controlled dose escalation study in 2 parts: a single ascending dose adaptive design with a food interaction arm, and a multiple ascending dose design. RARβ2 mRNA expression was evaluated in white blood cells.
    Results: At the highest single and multiple ascending doses (100 mg), no trends or clinically important differences were noted in the incidence or intensity of adverse events (AEs), serious AEs or other safety assessments with none leading to withdrawal from the study. The AEs were dry skin, rash, skin exfoliation, raised liver enzymes and eye disorders. There was an increase in mean maximum observed concentration and area under the plasma concentration-time curve up to 24 h showing a trend to subproportionality with dose. RARβ2 was upregulated by the investigational medicinal product in white blood cells.
    Conclusion: KCL-286 was well tolerated by healthy human participants following doses that exceeded potentially clinically relevant plasma exposures based on preclinical in vivo models. Target engagement shows the drug candidate activates its receptor. These findings support further development of KCL-286 as a novel oral treatment for SCI.
    MeSH term(s) Humans ; Male ; Healthy Volunteers ; Dose-Response Relationship, Drug ; Receptors, Retinoic Acid ; Area Under Curve ; Double-Blind Method ; Drugs, Investigational
    Chemical Substances retinoic acid receptor beta ; Receptors, Retinoic Acid ; Drugs, Investigational
    Language English
    Publishing date 2023-08-09
    Publishing country England
    Document type Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15854
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  2. Article ; Online: Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol.

    Mansouri, Anita / McGregor, Naomi / Dunn, Rachel / Dobbie, Sam / Holmes, Jane / Collins, Linda / Nicum, Shibani

    BMJ open

    2021  Volume 11, Issue 1, Page(s) e041463

    Abstract: Introduction: Patients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer ... ...

    Abstract Introduction: Patients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months.
    Methods and analysis: ETHICS AND DISSEMINATION: This study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150.
    Trial registration number: ISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.
    MeSH term(s) Clinical Trials, Phase II as Topic ; Female ; Humans ; Neoplasm Recurrence, Local/drug therapy ; Ovarian Neoplasms/drug therapy ; Phthalazines/therapeutic use ; Piperazines ; Quinazolines ; Randomized Controlled Trials as Topic
    Chemical Substances Phthalazines ; Piperazines ; Quinazolines ; cediranib (NQU9IPY4K9) ; olaparib (WOH1JD9AR8)
    Language English
    Publishing date 2021-01-15
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2020-041463
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  3. Article ; Online: Suicidal Intent and Method of Self-Harm: A Large-scale Study of Self-Harm Patients Presenting to a General Hospital.

    Haw, Camilla / Casey, Deborah / Holmes, Jane / Hawton, Keith

    Suicide & life-threatening behavior

    2015  Volume 45, Issue 6, Page(s) 732–746

    Abstract: Data from the Oxford Monitoring System for Attempted Suicide (2004-2011) were used to study hospital presentations for self-harm in which Suicidal Intent Scale (SIS) scores were obtained (N = 4,840). Regression of medians was used to control for the ... ...

    Abstract Data from the Oxford Monitoring System for Attempted Suicide (2004-2011) were used to study hospital presentations for self-harm in which Suicidal Intent Scale (SIS) scores were obtained (N = 4,840). Regression of medians was used to control for the confounding effect of age and gender. Higher estimated median SIS scores were associated with increasing age, male gender, self-poisoning versus self-injury, multiple methods of self-harm versus self-injury alone, use of gas (mainly carbon monoxide), dangerous methods of self-injury (including hanging, gunshot), and use of alcohol as part of the act. For self-poisoning patients, there was a correlation between the number of tablets taken and the total SIS score. Compared with self-poisoning with paracetamol and paracetamol-containing compounds, self-poisoning with antipsychotics was associated with a lower median SIS score while antidepressants had the same estimated median as paracetamol. Use of alcohol within 6 hours of self-harm was associated with lower SIS scores. In conclusion, certain methods of self-harm, particularly dangerous methods of self-injury and self-poisoning with gas, were associated with high intent and should alert clinicians to potential higher risk of suicide. However, apart from use of gas, suicidal intent cannot be inferred from type of drugs used for self-poisoning.
    MeSH term(s) Adolescent ; Adult ; Child ; Dangerous Behavior ; Female ; Hospitalization/statistics & numerical data ; Hospitals, General/methods ; Hospitals, General/statistics & numerical data ; Humans ; Intention ; Male ; Middle Aged ; Psychiatric Status Rating Scales ; Risk Assessment/methods ; Risk Factors ; Self-Injurious Behavior/classification ; Self-Injurious Behavior/epidemiology ; Self-Injurious Behavior/prevention & control ; Self-Injurious Behavior/psychology ; Suicidal Ideation ; Suicide, Attempted/prevention & control ; Suicide, Attempted/psychology ; Suicide, Attempted/statistics & numerical data ; United Kingdom/epidemiology
    Language English
    Publishing date 2015-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 750058-0
    ISSN 1943-278X ; 0047-4592 ; 0363-0234
    ISSN (online) 1943-278X
    ISSN 0047-4592 ; 0363-0234
    DOI 10.1111/sltb.12168
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  4. Article ; Online: Practicalities in running early-phase trials using the time-to-event continual reassessment method (TiTE-CRM) for interventions with long toxicity periods using two radiotherapy oncology trials as examples.

    van Werkhoven, Erik / Hinsley, Samantha / Frangou, Eleni / Holmes, Jane / de Haan, Rosemarie / Hawkins, Maria / Brown, Sarah / Love, Sharon B

    BMC medical research methodology

    2020  Volume 20, Issue 1, Page(s) 162

    Abstract: Background: Awareness of model-based designs for dose-finding studies such as the Continual Reassessment Method (CRM) is now becoming more commonplace amongst clinicians, statisticians and trial management staff. In some settings toxicities can occur a ... ...

    Abstract Background: Awareness of model-based designs for dose-finding studies such as the Continual Reassessment Method (CRM) is now becoming more commonplace amongst clinicians, statisticians and trial management staff. In some settings toxicities can occur a long time after treatment has finished, resulting in extremely long, interrupted, CRM design trials. The Time-to-Event CRM (TiTE-CRM), a modification to the original CRM, accounts for the timing of late-onset toxicities and results in shorter trial duration. In this article, we discuss how to design and deliver a trial using this method, from the grant application stage through to dissemination, using two radiotherapy trials as examples.
    Methods: The TiTE-CRM encapsulates the dose-toxicity relationship with a statistical model. The model incorporates observed toxicities and uses a weight to account for the proportion of completed follow-up of participants without toxicity. This model uses all available data to determine the next participant's dose and subsequently declare the maximum tolerated dose. We focus on two trials designed by the authors to illustrate practical issues when designing, setting up, and running such studies.
    Results: In setting up a TiTE-CRM trial, model parameters need to be defined and the time element involved might cause complications, therefore looking at operating characteristics through simulations is essential. At the grant application stage, we suggest resources to fund statisticians' time before funding is awarded and make recommendations for the level of detail to include in funding applications. While running the trial, close contact of all involved staff is required as a dose decision is made each time a participant is recruited. We suggest ways of capturing data in a timely manner and give example code in R for design and delivery of the trial. Finally, we touch upon dissemination issues while the trial is running and upon completion.
    Conclusion: Model-based designs can be complex. We hope this paper will help clinical trial teams to demystify the conduct of TiTE-CRM trials and be a starting point for using this methodology in practice.
    MeSH term(s) Dose-Response Relationship, Drug ; Humans ; Maximum Tolerated Dose ; Models, Statistical ; Neoplasms/drug therapy ; Neoplasms/radiotherapy ; Research Design
    Language English
    Publishing date 2020-06-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041362-2
    ISSN 1471-2288 ; 1471-2288
    ISSN (online) 1471-2288
    ISSN 1471-2288
    DOI 10.1186/s12874-020-01012-z
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  5. Article ; Online: Looking Back on Self-Poisoning: The Relationship between Depressed Mood and Reporting of Suicidal Intent in People Who Deliberately Self-Poison.

    Gjelsvik, Bergljot / Heyerdahl, Fridtjof / Holmes, Jane / Lunn, Daniel / Hawton, Keith

    Suicide & life-threatening behavior

    2016  Volume 47, Issue 2, Page(s) 228–241

    Abstract: Lifetime worst-point suicidality is associated with risk of subsequent death by suicide. Yet little is known about how people who deliberately self-poison (DSP) change their appraisal of suicidal intent of a single DSP episode over time. We assessed ... ...

    Abstract Lifetime worst-point suicidality is associated with risk of subsequent death by suicide. Yet little is known about how people who deliberately self-poison (DSP) change their appraisal of suicidal intent of a single DSP episode over time. We assessed whether suicidal intent for a single index episode of DSP changed over time and factors associated with such change. We studied 202 patients admitted for DSP (66.3% female, all Caucasian), 18-85 years old (M = 37.8, SD = 14.8), using a longitudinal design (0, 3, and 12 months). The primary outcome measure was change in suicidal intent for a single index DSP episode, analyzed using multilevel modeling. Wish to die and whether the episode was considered a suicide attempt increased significantly with depressed mood. Wish to die associated with the index episode also increased over time independently of depressed mood. No association with time or depressed mood was found for perceived likelihood of dying. Depressed mood was strongly associated with appraisal of suicidal intent associated with a DSP episode. In suicide risk assessment, reports of the nature and severity of past DSP should be interpreted in light of current mood.
    MeSH term(s) Adult ; Aged ; Depression/complications ; Depression/diagnosis ; Depression/psychology ; Female ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Poisoning/diagnosis ; Poisoning/psychology ; Psychiatric Status Rating Scales ; Risk Assessment/methods ; Risk Factors ; Self-Injurious Behavior/diagnosis ; Self-Injurious Behavior/psychology ; Suicidal Ideation ; Suicide/prevention & control ; Suicide/psychology
    Language English
    Publishing date 2016-07-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 750058-0
    ISSN 1943-278X ; 0047-4592 ; 0363-0234
    ISSN (online) 1943-278X
    ISSN 0047-4592 ; 0363-0234
    DOI 10.1111/sltb.12278
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  6. Article ; Online: Is There a Relationship between Suicidal Intent and Lethality in Deliberate Self-Poisoning?

    Gjelsvik, Bergljot / Heyerdahl, Fridtjof / Holmes, Jane / Lunn, Daniel / Hawton, Keith

    Suicide & life-threatening behavior

    2016  Volume 47, Issue 2, Page(s) 205–216

    Abstract: The relationship between suicidal intent and lethality of deliberate self-poisoning (DSP) episodes and their associations with suicide have yielded contradictory findings. The aims of this study were to investigate the association between patients' ... ...

    Abstract The relationship between suicidal intent and lethality of deliberate self-poisoning (DSP) episodes and their associations with suicide have yielded contradictory findings. The aims of this study were to investigate the association between patients' suicidal intent and independently rated lethality of DSP episodes, and whether the association changes over time. Eighty-nine DSP patients were investigated longitudinally. Self-reported suicidal intent, including perceived likelihood of dying, wish to die, and whether or not the DSP was considered a suicide attempt, was measured at the time of the index episode (t1), 3 months (t2), and 12 months (t3) later. Lethality was assessed independently by three clinical toxicologists. Lethality was significantly associated with patients' reported wish to die (p = .01) and perceived likelihood of dying (p = .04) at t1, but not at t2 and t3. No association was found between whether the episode was considered a suicide attempt or not and lethality at t1, t2, or t3. Lethality and suicidal intent should be considered as largely separate dimensions of self-harm. Clinicians should bear this in mind during clinical assessment, especially regarding historical information.
    MeSH term(s) Adult ; Female ; Humans ; Male ; Middle Aged ; Mortality ; Poisoning/mortality ; Poisoning/psychology ; Risk Assessment ; Self-Injurious Behavior/mortality ; Self-Injurious Behavior/psychology ; Suicidal Ideation ; Suicide, Attempted/prevention & control ; Suicide, Attempted/psychology
    Language English
    Publishing date 2016-07-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 750058-0
    ISSN 1943-278X ; 0047-4592 ; 0363-0234
    ISSN (online) 1943-278X
    ISSN 0047-4592 ; 0363-0234
    DOI 10.1111/sltb.12277
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  7. Article ; Online: Cost-utility analysis of molnupiravir plus usual care versus usual care alone as early treatment for community-based adults with COVID-19 and increased risk of adverse outcomes in the UK PANORAMIC trial.

    Png, May Ee / Harris, Victoria / Grabey, Jenna / Hart, Nigel David / Jani, Bhautesh Dinesh / Butler, Daniel / Carson-Stevens, Andrew / Coates, Maria / Cureton, Lucy / Dobson, Melissa / Dorward, Jienchi / Evans, Philip / Francis, Nick / Gbinigie, Oghenekome Abisoye / Hayward, Gail / Holmes, Jane / Hood, Kerenza / Khoo, Saye / Ahmed, Haroon /
    Lown, Mark / Mckenna, Micheal / Mort, Sam / Nguyen-Van-Tam, Jonathan / Rahman, Najib / Richards, Duncan B / Thomas, Nicholas / van Hecke, Oliver / Hobbs, Fd Richard / Little, Paul / Yu, Ly-Mee / Butler, Christopher C / Petrou, Stavros

    The British journal of general practice : the journal of the Royal College of General Practitioners

    2024  

    Abstract: Background: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations.: Aim: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among ... ...

    Abstract Background: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations.
    Aim: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over six months.
    Design and setting: Economic evaluation of the PANORAMIC trial in the UK.
    Method: A cost-utility analysis that adopted a UK National Health Service and personal social services perspective and a six-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement.
    Results: In the base case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] 445 to 453) and higher mean QALYs of 0.0055 (95% CI 0.004 to 0.007) than usual care (mean incremental cost per QALY of £81190). Sensitivity and subgroup analyses showed similar results, except those aged ≥75 years with a 55% probability of being cost-effective at a £30000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15000 per QALY threshold.
    Conclusion: Molnupiravir at the current cost of £513 per course is unlikely to be cost-effective relative to usual care over a six-month time horizon among mainly vaccinated COVID-19 patients at increased risk of adverse outcomes, except those aged ≥75 years.
    Language English
    Publishing date 2024-01-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 1043148-2
    ISSN 1478-5242 ; 0035-8797 ; 0960-1643
    ISSN (online) 1478-5242
    ISSN 0035-8797 ; 0960-1643
    DOI 10.3399/BJGP.2023.0444
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  8. Article ; Online: Early phase clinical trials extension to guidelines for the content of statistical analysis plans.

    Homer, Victoria / Yap, Christina / Bond, Simon / Holmes, Jane / Stocken, Deborah / Walker, Katrina / Robinson, Emily J / Wheeler, Graham / Brown, Sarah / Hinsley, Samantha / Schipper, Matthew / Weir, Christopher J / Rantell, Khadija / Prior, Thomas / Yu, Ly-Mee / Kirkpatrick, John / Bedding, Alun / Gamble, Carrol / Gaunt, Piers

    BMJ (Clinical research ed.)

    2022  Volume 376, Page(s) e068177

    MeSH term(s) Clinical Trials as Topic ; Data Analysis ; Guidelines as Topic
    Language English
    Publishing date 2022-02-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj-2021-068177
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  9. Article ; Online: A multicentre retrospective review of SABR reirradiation in rectal cancer recurrence.

    Johnstone, Philippa / Okonta, Leroy / Aitken, Katharine / Holmes, Jane / Harrison, Mark / Harji, Deena / O'Cathail, Sean M / Taylor, Claire / Tsang, Yat / Wing, Mark / Muirhead, Rebecca

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

    2021  Volume 162, Page(s) 1–6

    Abstract: Background and purpose: Locally recurrent rectal cancer (LRRC) is associated with considerable morbidity, poor quality of life and an overall survival of 9 months. The non-operative treatment of LRRC is an understudied area, there is no consensus on ... ...

    Abstract Background and purpose: Locally recurrent rectal cancer (LRRC) is associated with considerable morbidity, poor quality of life and an overall survival of 9 months. The non-operative treatment of LRRC is an understudied area, there is no consensus on management in this setting. We aim to perform a retrospective, multicentre analysis of patients treated with SABR reirradiation.
    Materials and methods: All patients were identified who received SABR re-irradiation for LRRC, at 3 UK centres, between August 2015 and September 2020. Eligible patients had pelvic recurrence and were either not suitable/opted not for surgery, or margin positive after exenturative surgery. Patients were treated with 30 Gy in 5 fractions and followed up with clinical review and CT scan at 3, 6, 12, 18 and 24 months.
    Results: 69 patients with 81 lesions were identified and median follow up was 28 months. Median progression free survival (PFS) and overall survival (OS) were 12.1 months (10.4, 17.7) and 38.7 months (28.9,-) respectively. 2-year OS was 0.77 (0.66, 0.89). 58.3% of deaths were as a result of consequences of local relapse. 42.6% of patients had local relapse at death or last follow up.
    Conclusion: Our outcomes are encouraging for a population who had R1 resections, refused or were refused surgery; as they are similar to those in surgical series. Prospective data including details of survival, local relapse and QOL; with an optimised SABR technique, is required to establish SABR as an alternative to surgery.
    MeSH term(s) Humans ; Lung Neoplasms/surgery ; Neoplasm Recurrence, Local/radiotherapy ; Neoplasm Recurrence, Local/surgery ; Prospective Studies ; Quality of Life ; Radiosurgery ; Re-Irradiation ; Rectal Neoplasms/radiotherapy ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2021-06-25
    Publishing country Ireland
    Document type Journal Article ; Multicenter Study
    ZDB-ID 605646-5
    ISSN 1879-0887 ; 0167-8140
    ISSN (online) 1879-0887
    ISSN 0167-8140
    DOI 10.1016/j.radonc.2021.06.030
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  10. Article ; Online: Challenges in implementing model-based phase I designs in a grant-funded clinical trials unit.

    Frangou, Eleni / Holmes, Jane / Love, Sharon / McGregor, Naomi / Hawkins, Maria

    Trials

    2017  Volume 18, Issue 1, Page(s) 620

    Abstract: Background: For a clinical trials unit to run its first model-based, phase I trial, the statistician, chief investigator, and trial manager must all acquire a new set of skills. These trials also require a different approach to funding and data ... ...

    Abstract Background: For a clinical trials unit to run its first model-based, phase I trial, the statistician, chief investigator, and trial manager must all acquire a new set of skills. These trials also require a different approach to funding and data collection.
    Challenges and discussion: From the statisticians' viewpoint, we highlight what is needed to move from running rule-based, early-phase trials to running a model-based phase I study as we experienced it in our trials unit located in the United Kingdom. Our example is CHARIOT, a dose-finding trial using the time-to-event continual reassessment method. It consists of three stages and aims to discover the maximum tolerated dose of the combination of radiotherapy, chemotherapy, and the ataxia telangiectasia mutated Rad3-related inhibitor M6620 (previously known as VX-970) in patients with oesophageal cancer. We present the challenges we faced in designing this trial and how we overcame them as a way of demystifying the conduct of a model-based trial in a grant-funded clinical trials unit.
    Conclusions: Although we appreciate that undertaking model-based trials requires additional time and effort, they are feasible to implement and, once suitable tools such as guiding publications and document templates become available, the design and set-up process will be easier and more efficient.
    MeSH term(s) Clinical Trials, Phase I as Topic/methods ; Combined Modality Therapy ; Esophageal Neoplasms/therapy ; Humans ; Isoxazoles/administration & dosage ; Maximum Tolerated Dose ; Pyrazines/administration & dosage ; Research Design
    Chemical Substances Isoxazoles ; Pyrazines ; berzosertib (L423PRV3V3)
    Language English
    Publishing date 2017-12-28
    Publishing country England
    Document type Letter
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-017-2389-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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