Citation: Scientific Reports. 2020, 10(1), 342
Author: Taha Elmetwali, Asmaa Salman, Wenbin Wei, Syed A Hussain, Lawrence S Young, Daniel H Palmer
Abstract: In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.
Link to PubMed record
Wednesday, 29 January 2020
CCC publication: Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study
Citation: Blood. 2020 Jan 13[Online ahead of print]
Author: Richard Dillon, Robert K Hills, Sylvie D Freeman, Nicola Potter, Jelena Jovanovic, Adam Ivey, Anju Shankar Kanda, Manohursingh Runglall, Nicola Foot, Mikel Valganon, Asim Khwaja, Jamie Cavenagh, Matthew L Smith, Hans Beier Ommen, Ulrik Overgaard, Mike Dennis, Steven Knapper, Harpreet Kaur, David C Taussig, Priyanka Mehta, Kavita Raj, Igor Novitzky-Basso, Emmanouil Nikolousis, Robert D Danby, Pramila Krishnamurthy, Kate Hill, Damian Finnegan, Samah Alimam, Erin Hurst, Peter Johnson, Anjum Bashir Khan, Rahuman Salim, Charles F Craddock, Ruth Lilian Spearing, Amanda Frances Gilkes, Rosemary E Gale, Alan Kenneth Burnett, Nigel H Russell, David Grimwade
Abstract: Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (AML) who undergo allogeneic stem cell transplantation (alloSCT) and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry (FCM) prior to alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays which have far greater sensitivity. We analysed pre-transplant blood and bone marrow samples by reverse-transcription polymerase chain reaction (RT-qPCR) in 107 patients with NPM1 mutant AML enrolled in the UK National Cancer Research Institute (NCRI) AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies / 105 ABL in the PB and <1000 copies in the BM) and high levels of MRD had an estimated 2y overall survival (OS) of 83%, 63% and 13% respectively (p<0.0001). Focussing on patients with low level MRD prior to alloSCT, those with FLT3 ITD had significantly poorer outcome (hazard ratio, HR, 6.14, p=0.01). Combining these variables was highly prognostic, dividing patients into two groups with 2y OS of 17% and 82% (HR 13.2, p<0.0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y OS 56% vs 96%, HR 3.24, p=0.0005) and in MRD positive patients (2y OS 34% vs 100%, HR 3.78, p=0.003) but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).
Link to PubMed record
Author: Richard Dillon, Robert K Hills, Sylvie D Freeman, Nicola Potter, Jelena Jovanovic, Adam Ivey, Anju Shankar Kanda, Manohursingh Runglall, Nicola Foot, Mikel Valganon, Asim Khwaja, Jamie Cavenagh, Matthew L Smith, Hans Beier Ommen, Ulrik Overgaard, Mike Dennis, Steven Knapper, Harpreet Kaur, David C Taussig, Priyanka Mehta, Kavita Raj, Igor Novitzky-Basso, Emmanouil Nikolousis, Robert D Danby, Pramila Krishnamurthy, Kate Hill, Damian Finnegan, Samah Alimam, Erin Hurst, Peter Johnson, Anjum Bashir Khan, Rahuman Salim, Charles F Craddock, Ruth Lilian Spearing, Amanda Frances Gilkes, Rosemary E Gale, Alan Kenneth Burnett, Nigel H Russell, David Grimwade
Abstract: Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (AML) who undergo allogeneic stem cell transplantation (alloSCT) and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry (FCM) prior to alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays which have far greater sensitivity. We analysed pre-transplant blood and bone marrow samples by reverse-transcription polymerase chain reaction (RT-qPCR) in 107 patients with NPM1 mutant AML enrolled in the UK National Cancer Research Institute (NCRI) AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies / 105 ABL in the PB and <1000 copies in the BM) and high levels of MRD had an estimated 2y overall survival (OS) of 83%, 63% and 13% respectively (p<0.0001). Focussing on patients with low level MRD prior to alloSCT, those with FLT3 ITD had significantly poorer outcome (hazard ratio, HR, 6.14, p=0.01). Combining these variables was highly prognostic, dividing patients into two groups with 2y OS of 17% and 82% (HR 13.2, p<0.0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y OS 56% vs 96%, HR 3.24, p=0.0005) and in MRD positive patients (2y OS 34% vs 100%, HR 3.78, p=0.003) but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).
Link to PubMed record
CCC publication: Digitising a consultant radiographer led palliative radiotherapy service,
Citation: Radiography. 2020, 26(Sup1), S22
Author: Conor Fitzpatrick,
Author: Conor Fitzpatrick,
CCC publication: Improving patient pathways in head and neck cancer at a UK Cancer Centre. Results of a dietetic pre-treatment project (DPP)
Citation: Clinical Nutrition ESPEN. 2020, 35, 250
Author: Parr K.; Johnson F.; Langley N.; Richardson P.
Author: Parr K.; Johnson F.; Langley N.; Richardson P.
CCC publication: Evaluation of erectile potency and radiation dose to the penile bulb using image guided radiotherapy in the CHHiP trial,
Citation: Clinical and Translational Radiation Oncology. 2019 Dec 31, 21, 77-84. eCollection Mar 2020
Author: J. Murray, S. Gulliford, C. Griffin, A. Wilkins, I. Syndikus, J. Staffurth, M. Panades, C. Scrase, C. Parker, V. Khoo, J. Dean, H. Mayles, P. Mayles, S. Thomas, O. Naismith, H. Mossop, C. Cruickshank, E. Hall, D. Dearnaley
Abstract: Background and purpose: The penile bulb (PB) dose may be critical in development of post prostate radiotherapy erectile dysfunction (ED). This study aimed to generate PB dose constraints based on dose-volume histograms (DVHs) in patients treated with prostate radiotherapy, and to identify clinical and dosimetric parameters that predict the risk of ED post prostate radiotherapy.
Materials and methods: Penile bulb DVHs were generated for 276 patients treated within the randomised IGRT substudy of the multicentre randomised trial, CHHiP. Incidence of ED in relation to dose and randomised IGRT groups were evaluated using Wilcoxon rank sum, Chi-squared test and atlases of complication incidence. Youden index was used to find dose-volume constraints that discriminated for ED. Multivariate analysis (MVA) of effect of dosimetry, clinical and patient-related variables was performed.
Results: Reduced treatment margins using IGRT (IGRT-R) produced significantly reduced mean PB dose compared with standard margins (IGRT-S) (median: 25 Gy (IGRT-S) versus 11 Gy (IGRT-R); p < 0.0001). Significant difference in both mean (median: 23 Gy (ED) vs. 18 Gy (no ED); p = 0.011) and maximum (median: 59 Gy (ED) vs. 52 Gy (no ED); p = 0.018) PB doses between those with and without clinician reported ED were identified. Mean PB dose cut-point for ED was derived at around 20 Gy. On MVA, PB mean dose and age predicted for impotence.
Conclusion: PB dose appears predictive of post-radiotherapy ED with calculated threshold mean dose of around 20 Gy, substantially lower than published recommendations. IGRT-R enables favourable PB dosimetry and can be recommended provided prostate coverage is not compromised.
Keywords: Erectile dysfunction; Image-guided radiotherapy; Penile bulb; Prostate.
Link to PubMed record
Author: J. Murray, S. Gulliford, C. Griffin, A. Wilkins, I. Syndikus, J. Staffurth, M. Panades, C. Scrase, C. Parker, V. Khoo, J. Dean, H. Mayles, P. Mayles, S. Thomas, O. Naismith, H. Mossop, C. Cruickshank, E. Hall, D. Dearnaley
Abstract: Background and purpose: The penile bulb (PB) dose may be critical in development of post prostate radiotherapy erectile dysfunction (ED). This study aimed to generate PB dose constraints based on dose-volume histograms (DVHs) in patients treated with prostate radiotherapy, and to identify clinical and dosimetric parameters that predict the risk of ED post prostate radiotherapy.
Materials and methods: Penile bulb DVHs were generated for 276 patients treated within the randomised IGRT substudy of the multicentre randomised trial, CHHiP. Incidence of ED in relation to dose and randomised IGRT groups were evaluated using Wilcoxon rank sum, Chi-squared test and atlases of complication incidence. Youden index was used to find dose-volume constraints that discriminated for ED. Multivariate analysis (MVA) of effect of dosimetry, clinical and patient-related variables was performed.
Results: Reduced treatment margins using IGRT (IGRT-R) produced significantly reduced mean PB dose compared with standard margins (IGRT-S) (median: 25 Gy (IGRT-S) versus 11 Gy (IGRT-R); p < 0.0001). Significant difference in both mean (median: 23 Gy (ED) vs. 18 Gy (no ED); p = 0.011) and maximum (median: 59 Gy (ED) vs. 52 Gy (no ED); p = 0.018) PB doses between those with and without clinician reported ED were identified. Mean PB dose cut-point for ED was derived at around 20 Gy. On MVA, PB mean dose and age predicted for impotence.
Conclusion: PB dose appears predictive of post-radiotherapy ED with calculated threshold mean dose of around 20 Gy, substantially lower than published recommendations. IGRT-R enables favourable PB dosimetry and can be recommended provided prostate coverage is not compromised.
Keywords: Erectile dysfunction; Image-guided radiotherapy; Penile bulb; Prostate.
Link to PubMed record
CCC publication: CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial.
Citation: Trials. 2020, 21(1), 89
Author: Rob Coleman, Janet Brown, Emma Rathbone, Louise Flanagan, Amber Reid, Jessica Kendall, Sacha Howell, Chris Twelves, Carlo Palmieri, Anjana Anand, Iain MacPherson, Sarah Brown
Abstract: Background: A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.
Methods/design: CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.
Discussion: The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.
Trial registration: ISRCTN, ISRCTN92755158, Registered on 17 February 2016.
Keywords: Bone metastases; Bone turnover markers; Breast cancer; Capecitabine; Radium-223
Link to PubMed record
Author: Rob Coleman, Janet Brown, Emma Rathbone, Louise Flanagan, Amber Reid, Jessica Kendall, Sacha Howell, Chris Twelves, Carlo Palmieri, Anjana Anand, Iain MacPherson, Sarah Brown
Abstract: Background: A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.
Methods/design: CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.
Discussion: The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.
Trial registration: ISRCTN, ISRCTN92755158, Registered on 17 February 2016.
Keywords: Bone metastases; Bone turnover markers; Breast cancer; Capecitabine; Radium-223
Link to PubMed record
CCC publication: Development of an orthotopic syngeneic murine model of colorectal cancer for use in translational research
Citation: Laboratory Animals. 2019, 53(6), 598-609
Author: Evans J.P. (jpevans@liverpool.ac.uk); Sutton P.A.; Palmer D.H.; Winiarski B.K.; Goldring C.E.; Kitteringham N.R.; Ressel L.; Duckworth C.A.; Pritchard D.M.
Abstract: Improving outcomes in colorectal cancer requires more accurate in vivo modelling of the disease in humans, allowing more reliable pre-clinical assessment of potential therapies. Novel imaging techniques are necessary to improve the longitudinal assessment of disease burden in these models, reducing the number of animals required for translational studies. This report describes the development of an immune-competent syngeneic orthotopic murine model of colorectal cancer, utilising caecal implantation of CT26 cells stably transfected with the luciferase gene into immune-competent BALB/c mice, allowing serial bioluminescent imaging of cancer progression. Luminescence in the stably transfected CT26 cell line, after pre-conditioning in the flank of a BALB/c mouse, accurately reflected cell viability and resulted in primary caecal tumours in five of eight (63%) mice in the initial pilot study following caecal injection. Luminescent signal continued to increase throughout the study period with one mouse (20%) developing a liver metastasis. Histopathological assessment confirmed tumours to be consistent with a poorly differentiated adenocarcinoma. We have now performed this technique in 68 immune-competent BALB/c mice. There have been no complications from the procedure or peri-operative deaths, with primary tumours developing in 44 (65%) mice and liver metastases in nine (20%) of these. This technique provides an accurate model of colorectal cancer with tumours developing in the correct microenvironment and metastasising to the liver with a similar frequency to that seen in patients presenting with colorectal cancer, with serial bioluminescent reducing the murine numbers required in studies by removing the need for cull for assessment of disease burden.
KEYWORDS: Colorectal cancer; bioluminescent imaging; orthotopic syngeneic model
Link to PubMed record
Author: Evans J.P. (jpevans@liverpool.ac.uk); Sutton P.A.; Palmer D.H.; Winiarski B.K.; Goldring C.E.; Kitteringham N.R.; Ressel L.; Duckworth C.A.; Pritchard D.M.
Abstract: Improving outcomes in colorectal cancer requires more accurate in vivo modelling of the disease in humans, allowing more reliable pre-clinical assessment of potential therapies. Novel imaging techniques are necessary to improve the longitudinal assessment of disease burden in these models, reducing the number of animals required for translational studies. This report describes the development of an immune-competent syngeneic orthotopic murine model of colorectal cancer, utilising caecal implantation of CT26 cells stably transfected with the luciferase gene into immune-competent BALB/c mice, allowing serial bioluminescent imaging of cancer progression. Luminescence in the stably transfected CT26 cell line, after pre-conditioning in the flank of a BALB/c mouse, accurately reflected cell viability and resulted in primary caecal tumours in five of eight (63%) mice in the initial pilot study following caecal injection. Luminescent signal continued to increase throughout the study period with one mouse (20%) developing a liver metastasis. Histopathological assessment confirmed tumours to be consistent with a poorly differentiated adenocarcinoma. We have now performed this technique in 68 immune-competent BALB/c mice. There have been no complications from the procedure or peri-operative deaths, with primary tumours developing in 44 (65%) mice and liver metastases in nine (20%) of these. This technique provides an accurate model of colorectal cancer with tumours developing in the correct microenvironment and metastasising to the liver with a similar frequency to that seen in patients presenting with colorectal cancer, with serial bioluminescent reducing the murine numbers required in studies by removing the need for cull for assessment of disease burden.
KEYWORDS: Colorectal cancer; bioluminescent imaging; orthotopic syngeneic model
Link to PubMed record
Friday, 24 January 2020
WUTH publication: 'Tax-otsubo': stress cardiomyopathy following an encounter with the Inland Revenue
Citation: BMJ Case Reports. 2020, 13(1), e232225
Author: Roach MW, Currie P
Abstract: An 89-year-old man developed chest pain and palpitations shortly after finishing a stressful 40 min phone call to HM Revenue and Customs. After admission to the emergency department, he had a cardiovascular collapse followed soon after by a cardiac arrest due to ventricular fibrillation (VF). The troponin T was elevated and his ECG showed extensive deep T wave inversion with prolongation of the QT interval. A portable hand-held ultrasound device (VScan; GE Healthcare) was used to demonstrate classical apical ballooning of the left ventricular apex indicating a diagnosis of takotsubo stress cardiomyopathy. Shortly following admission to the cardiac care unit, he had a further episode of VF, which was successfully defibrillated. A coronary angiogram was performed, which was normal. He was treated with a short course of benzodiazepines. He was discharged after 8 days without any neurological deficit. His echocardiogram subsequently showed complete resolution of the abnormalities of the left ventricular function.
© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: arrhythmias; clinical diagnostic tests; heart failure
Link to PubMed record
Author: Roach MW, Currie P
Abstract: An 89-year-old man developed chest pain and palpitations shortly after finishing a stressful 40 min phone call to HM Revenue and Customs. After admission to the emergency department, he had a cardiovascular collapse followed soon after by a cardiac arrest due to ventricular fibrillation (VF). The troponin T was elevated and his ECG showed extensive deep T wave inversion with prolongation of the QT interval. A portable hand-held ultrasound device (VScan; GE Healthcare) was used to demonstrate classical apical ballooning of the left ventricular apex indicating a diagnosis of takotsubo stress cardiomyopathy. Shortly following admission to the cardiac care unit, he had a further episode of VF, which was successfully defibrillated. A coronary angiogram was performed, which was normal. He was treated with a short course of benzodiazepines. He was discharged after 8 days without any neurological deficit. His echocardiogram subsequently showed complete resolution of the abnormalities of the left ventricular function.
© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: arrhythmias; clinical diagnostic tests; heart failure
Link to PubMed record
Thursday, 9 January 2020
Notification of scheduled maintenance to BMJ websites
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BMJ runs a policy of continuous improvement in its hosting environments and we will be using this time to complete a project to migrate our hosting services to a more modern, scalable platform. This will result in an improvement in the reliability, robustness and performance of BMJ websites. Thank you for your patience and understanding. If you have any questions, please speak to your account manager or contact support.bmj.com. |
Friday, 3 January 2020
WUTH publication: An investigation into the avoidability of adverse drug reactions using the LAAT and modified Hallas tools
Citation: Medicine (Baltimore). 2020, 99(1), e18569
Author: Danjuma MI, Shokri SA, Abubeker IY, Malik AE, Abdallah IMH, Shafei MNE, Fatima H, Mahmoud M, Hussain T, Maghoub Y, Sajid J, Zouki ANE
Abstract: An adverse drug reactions avoidability tool called the Liverpool ADR avoidability assessment tool (LAAT) was recently developed (for research purposes), and subsequently validated with mixed interrater reliability (IRR). We investigated the comparative IRR of this tool in an inpatient cohort to ascertain its practical application in this setting.The patient population was comprised of 44 ADR drug pairs drawn from an observational prospective cohort of patents with ADR attending a Weill Cornell Medicine-affiliated tertiary medical Centre in Doha Qatar (Hamad General Hospital). Using the LAAT, and modified Hallas tools, 4 independent raters (2 Clinical Pharmacologists, and 2 General Physicians) assessed and scored the 44 ADR-drug pairs. Agreement proportions between the rating pairs were evaluated as well individual/overall kappa statistics and intraclass correlation coefficients. We evaluated the weight of each of the 7 questions on the LAAT tool to ascertain its determinative role.Across 44 ADR-drug pairs, the overall median Fleiss kappa using the LAAT, and modified Hallas tools were 0.67 (interquartile range (IQR) 0.55, 0.76), 0.36 (IQR, 0.23-0.71) respectively. The overall percentage pairwise agreement with the LAAT and modified Hallas tools were 78.5%, and 62.2% respectively. Exact pairwise agreement occurred in 37 out of 44 (range 0.71-1), and 27 of 44 (0.53-0.77) ADR-drug pairs using the LAAT and modified Hallas tools respectively. Using the LAAT tool, the overall intraclass correlation coefficient was 0.68 (CI 0.55, 0.79), and 0.37 (CI 0.22, 0.53) with the modified Hallas tool.We report a higher proportion of "possible" and "definite" avoidability outcomes of adverse drug reactions compared with the modified Hallas, or that reported by developers of the LAAT tool. Although initially developed for research purposes, our report has suggested for the first time a potential applicability of this tool in clinical environment as well.
Link to PubMed record
Author: Danjuma MI, Shokri SA, Abubeker IY, Malik AE, Abdallah IMH, Shafei MNE, Fatima H, Mahmoud M, Hussain T, Maghoub Y, Sajid J, Zouki ANE
Abstract: An adverse drug reactions avoidability tool called the Liverpool ADR avoidability assessment tool (LAAT) was recently developed (for research purposes), and subsequently validated with mixed interrater reliability (IRR). We investigated the comparative IRR of this tool in an inpatient cohort to ascertain its practical application in this setting.The patient population was comprised of 44 ADR drug pairs drawn from an observational prospective cohort of patents with ADR attending a Weill Cornell Medicine-affiliated tertiary medical Centre in Doha Qatar (Hamad General Hospital). Using the LAAT, and modified Hallas tools, 4 independent raters (2 Clinical Pharmacologists, and 2 General Physicians) assessed and scored the 44 ADR-drug pairs. Agreement proportions between the rating pairs were evaluated as well individual/overall kappa statistics and intraclass correlation coefficients. We evaluated the weight of each of the 7 questions on the LAAT tool to ascertain its determinative role.Across 44 ADR-drug pairs, the overall median Fleiss kappa using the LAAT, and modified Hallas tools were 0.67 (interquartile range (IQR) 0.55, 0.76), 0.36 (IQR, 0.23-0.71) respectively. The overall percentage pairwise agreement with the LAAT and modified Hallas tools were 78.5%, and 62.2% respectively. Exact pairwise agreement occurred in 37 out of 44 (range 0.71-1), and 27 of 44 (0.53-0.77) ADR-drug pairs using the LAAT and modified Hallas tools respectively. Using the LAAT tool, the overall intraclass correlation coefficient was 0.68 (CI 0.55, 0.79), and 0.37 (CI 0.22, 0.53) with the modified Hallas tool.We report a higher proportion of "possible" and "definite" avoidability outcomes of adverse drug reactions compared with the modified Hallas, or that reported by developers of the LAAT tool. Although initially developed for research purposes, our report has suggested for the first time a potential applicability of this tool in clinical environment as well.
Link to PubMed record
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