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Thomas Keegan - One of the best experts on this subject based on the ideXlab platform.

  • o5c 5 sarin exposures in a cohort of british military participants in human experimental research at Porton Down 1945 1987
    Occupational and Environmental Medicine, 2019
    Co-Authors: Thomas Keegan, Lucy M Carpenter, C Brooks, T Langdon, K M Venables
    Abstract:

    Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down, near Salisbury, is the UK’s centre for research on chemical warfare. Since WWI, a programme of experiments involving approximately 30 000 participants drawn from the UK armed services has been undertaken there. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data in a cohort of servicemen who attended Porton Down. Methods We have used existing data on exposures to UK servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans, all between 1945 and 1987. Of the 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For inhalation tests, assessed by changes in red blood cell cholinesterase median inhibition for was 41% (IQR 24%–51%), with a maximum of 87%. For dermal exposures, assessed by changes in unspecified cholinesterase, median inhibition was 22% (IQR 10%–37%), with a maximum inhibition of 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength f the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less apparent when protection was present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans. Acknowledgement We thank Nicola Fear and Gemma Archer, our collaborators in new work on these data, for their input.

  • p 2 01 epidemiological studies of the Porton Down veterans an update of cancer incidence and mortality to 2018
    Occupational and Environmental Medicine, 2019
    Co-Authors: Gemma Archer, Thomas Keegan, Claire Brooks, Lucy M Carpenter, K M Venables, Nicola T Fear
    Abstract:

    Introduction An update to the Porton Down Veterans Cohort study is planned for 2018–2021. Background Chemical warfare agents continue to be deployed by rogue states and terrorists, e.g. in Syria, Iraq, Tokyo, and Salisbury UK, yet their impact on long-term health is largely unknown. The Porton Down cohort comprises of 18 276 men who took part in the ‘human volunteer programme’ of chemical warfare agent research at Porton Down, UK, between 1941 to 1989, and a comparison group of 17 600 men who also served in the military. An original study linked veterans’ records to national registry data on cancer incidence and mortality up to 2004. By the end of 2004, 7306 of the Porton Down veterans and 6900 of the comparison cohort had died. The results showed Porton Down veterans had no overall excess of cancers (rate ratio (RR)=1.00, 95% CI 0.95–1.05) and a small (6%) excess of all-cause mortality (RR=1.06, 1.03–1.10) when compared with non-Porton Down veterans. Porton Down veterans had higher rates of certain cancers (e.g. ill-defined malignant neoplasms, and in situ neoplasms) and specific causes of death (e.g. genitourinary, circulatory and external causes). Objectives The updated study aims to replicate the original analyses but with an additional 15 years of follow-up – estimated to increase the number of deaths available for study to c 22 200. This will improve statistical power, allowing exposures and outcomes of interest from prior literature to be examined at a level of detail not possible in the original study, e.g. nerve agent antidotes, riot control agents, neurological mortality, and rarer cancers. Implications Greater understanding of the long-term risks associated with exposure to chemical agents could lead to raised awareness among policy makers and health care providers, leading to improved diagnosis and quality of care. Conflict of interest None

  • sarin exposures in a cohort of british military participants in human experimental research at Porton Down 1945 1987
    Annals of Work Exposures and Health, 2018
    Co-Authors: Thomas Keegan, Lucy M Carpenter, C Brooks, T Langdon, K M Venables
    Abstract:

    Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK’s centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. Methods In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28–51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

  • dermal exposures to sarin in military veterans at Porton Down
    ISEE Conference Abstracts, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, T Langdon, S Walker, Lm Carpenter, K M Venables
    Abstract:

    Background The modification of dermal exposures by clothing, which may either protect from exposure or increase its effect, is of considerable interest. Here, we describe early analyses of the effects of dermal exposures to the nerve agent sarin, using data drawn from our previous cohort study of military veterans of chemical tests at Porton Down between, 1939-1989. Methods Data on exposures were abstracted from the Porton Down historical archive. For each nerve agent test we abstracted data on date and type of test, the principal chemical(s) used and exposure intensity, duration and route. We also noted the presence of exposure modifiers. Maximum percentage change in the following cholinesterase (ChE) measures were abstracted or calculated: unspecified, whole blood, plasma and/or red blood cell (RBC) ChE. Results 3597 veterans were recorded as involved in 4299 tests with nerve agents, 1945-1987. The most tested nerve agent was sarin: 2980 veterans were involved in 3511 tests. 288 sarin exposures were dermal (9.6%) and most of those were modified physically, eg by clothing (188; 65%). Dermal sarin tests took place 1951 - 1953. Quantity of exposure to dermal sarin was measured for 273 tests and ranged from 0.13 to 300 mg. Applied exposures were higher in tests with modification (IQR 200-300 mg with modification and 0.28-8 mg without). Change in ChE activity was available for 279 dermal sarin tests (97%). The median change was -22% (IQR -10 to - 37%, range +12.5 to -99%). The median without modification was -4.5% (IQR 0 to -13%) and -31% (IQR -19 to -46%) with modification. Conclusions The quantity of dermal exposure to sarin influenced effect. However, modifier use may be confounded by exposure so further investigation of the relationships between exposure, effect, and modification will be carried out.

  • assessment of exposure to sarin in military veterans at Porton Down
    Occupational and Environmental Medicine, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, Lucy M Carpenter, T Langdon, S Walker, K M Venables
    Abstract:

    Objectives Mortality and cancer incidence was recently examined in a cohort of >18 000 veterans of tests at Porton Down, 1941–89. Here we describe exposures to the nerve agent, sarin, and document the use of exposure or effect modifiers. Methods Data were abstracted from the Porton Down historical archive. Specific chemical names and the test dates were abstracted. For nerve agents information was also abstracted on modifiers (eg, respirators or protective chemicals). Pre-test and maximum change in cholinesterase (ChE) was calculated for unspecified, whole blood, plasma, and/or red blood cell (RBC) ChE. Results A total 3597 veterans were recorded in 4299 nerve agent tests 1945-87. Sarin was the most commonly-tested nerve agent (2980 veterans; 3511 tests). Most sarin tests were by the inhalation route (85%), 8% were dermal, 3% ocular. 53% of sarin tests were unprotected. Of the remainder, 30% involved physical protection (eg, respirator), 21% a chemical modifier (eg, pyridostigmine). Median exposure intensity was 12 mg.min/m 3 for unprotected inhalation tests (IQR 5.1–14.8 mg.min/m 3 ), 10.7 mg.min/m3 for tests with physical protection (IQR 7.4–13.9 mg.min/m 3 ). The median unprotected dermal exposure was 0.49 mg (IQR 0.2–8 mg) and 250 mg for protected dermal exposures (IQR 200–300 mg). Median RBC ChE activity decreased with increasing sarin exposure (n = 712 tests); this decrease was of a similar magnitude irrespective of protection status. Conclusions Sarin was the nerve agent most frequently tested on veterans at Porton Down. Availability of data on exposure intensity has allowed quantitative assessment of the effect of physical and chemical modifiers.

Lucy M Carpenter - One of the best experts on this subject based on the ideXlab platform.

  • p 2 01 epidemiological studies of the Porton Down veterans an update of cancer incidence and mortality to 2018
    Occupational and Environmental Medicine, 2019
    Co-Authors: Gemma Archer, Thomas Keegan, Claire Brooks, Lucy M Carpenter, K M Venables, Nicola T Fear
    Abstract:

    Introduction An update to the Porton Down Veterans Cohort study is planned for 2018–2021. Background Chemical warfare agents continue to be deployed by rogue states and terrorists, e.g. in Syria, Iraq, Tokyo, and Salisbury UK, yet their impact on long-term health is largely unknown. The Porton Down cohort comprises of 18 276 men who took part in the ‘human volunteer programme’ of chemical warfare agent research at Porton Down, UK, between 1941 to 1989, and a comparison group of 17 600 men who also served in the military. An original study linked veterans’ records to national registry data on cancer incidence and mortality up to 2004. By the end of 2004, 7306 of the Porton Down veterans and 6900 of the comparison cohort had died. The results showed Porton Down veterans had no overall excess of cancers (rate ratio (RR)=1.00, 95% CI 0.95–1.05) and a small (6%) excess of all-cause mortality (RR=1.06, 1.03–1.10) when compared with non-Porton Down veterans. Porton Down veterans had higher rates of certain cancers (e.g. ill-defined malignant neoplasms, and in situ neoplasms) and specific causes of death (e.g. genitourinary, circulatory and external causes). Objectives The updated study aims to replicate the original analyses but with an additional 15 years of follow-up – estimated to increase the number of deaths available for study to c 22 200. This will improve statistical power, allowing exposures and outcomes of interest from prior literature to be examined at a level of detail not possible in the original study, e.g. nerve agent antidotes, riot control agents, neurological mortality, and rarer cancers. Implications Greater understanding of the long-term risks associated with exposure to chemical agents could lead to raised awareness among policy makers and health care providers, leading to improved diagnosis and quality of care. Conflict of interest None

  • o5c 5 sarin exposures in a cohort of british military participants in human experimental research at Porton Down 1945 1987
    Occupational and Environmental Medicine, 2019
    Co-Authors: Thomas Keegan, Lucy M Carpenter, C Brooks, T Langdon, K M Venables
    Abstract:

    Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down, near Salisbury, is the UK’s centre for research on chemical warfare. Since WWI, a programme of experiments involving approximately 30 000 participants drawn from the UK armed services has been undertaken there. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data in a cohort of servicemen who attended Porton Down. Methods We have used existing data on exposures to UK servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans, all between 1945 and 1987. Of the 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For inhalation tests, assessed by changes in red blood cell cholinesterase median inhibition for was 41% (IQR 24%–51%), with a maximum of 87%. For dermal exposures, assessed by changes in unspecified cholinesterase, median inhibition was 22% (IQR 10%–37%), with a maximum inhibition of 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength f the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less apparent when protection was present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans. Acknowledgement We thank Nicola Fear and Gemma Archer, our collaborators in new work on these data, for their input.

  • sarin exposures in a cohort of british military participants in human experimental research at Porton Down 1945 1987
    Annals of Work Exposures and Health, 2018
    Co-Authors: Thomas Keegan, Lucy M Carpenter, C Brooks, T Langdon, K M Venables
    Abstract:

    Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK’s centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. Methods In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28–51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

  • assessment of exposure to sarin in military veterans at Porton Down
    Occupational and Environmental Medicine, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, Lucy M Carpenter, T Langdon, S Walker, K M Venables
    Abstract:

    Objectives Mortality and cancer incidence was recently examined in a cohort of >18 000 veterans of tests at Porton Down, 1941–89. Here we describe exposures to the nerve agent, sarin, and document the use of exposure or effect modifiers. Methods Data were abstracted from the Porton Down historical archive. Specific chemical names and the test dates were abstracted. For nerve agents information was also abstracted on modifiers (eg, respirators or protective chemicals). Pre-test and maximum change in cholinesterase (ChE) was calculated for unspecified, whole blood, plasma, and/or red blood cell (RBC) ChE. Results A total 3597 veterans were recorded in 4299 nerve agent tests 1945-87. Sarin was the most commonly-tested nerve agent (2980 veterans; 3511 tests). Most sarin tests were by the inhalation route (85%), 8% were dermal, 3% ocular. 53% of sarin tests were unprotected. Of the remainder, 30% involved physical protection (eg, respirator), 21% a chemical modifier (eg, pyridostigmine). Median exposure intensity was 12 mg.min/m 3 for unprotected inhalation tests (IQR 5.1–14.8 mg.min/m 3 ), 10.7 mg.min/m3 for tests with physical protection (IQR 7.4–13.9 mg.min/m 3 ). The median unprotected dermal exposure was 0.49 mg (IQR 0.2–8 mg) and 250 mg for protected dermal exposures (IQR 200–300 mg). Median RBC ChE activity decreased with increasing sarin exposure (n = 712 tests); this decrease was of a similar magnitude irrespective of protection status. Conclusions Sarin was the nerve agent most frequently tested on veterans at Porton Down. Availability of data on exposure intensity has allowed quantitative assessment of the effect of physical and chemical modifiers.

  • cancer morbidity in british military veterans included in chemical warfare agent experiments at Porton Down cohort study
    BMJ, 2009
    Co-Authors: Lucy M Carpenter, Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, Mark J Nieuwenhuijsen, T Langdon, L Linsell, V Beral
    Abstract:

    OBJECTIVE: To determine cancer morbidity in members of the armed forces who took part in tests of chemical warfare agents from 1941 to 1989. DESIGN: Historical cohort study, with cohort members followed up to December 2004. DATA SOURCE: Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. PARTICIPANTS: All veterans included in the cohort study of mortality, excluding those known to have died or been lost to follow-up before 1 January 1971 when the UK cancer registration system commenced: 17,013 male members of the UK armed forces who took part in tests (Porton Down veterans) and a similar group of 16,520 men who did not (non-Porton Down veterans). MAIN OUTCOME MEASURES: Cancer morbidity in each group of veterans; rate ratios, with 95% confidence intervals, adjusted for age group and calendar period. RESULTS: 3457 cancers were reported in the Porton Down veterans compared with 3380 cancers in the non-Porton Down veterans. While overall cancer morbidity was the same in both groups (rate ratio 1.00, 95% confidence interval 0.95 to 1.05), Porton Down veterans had higher rates of ill defined malignant neoplasms (1.12, 1.02 to 1.22), in situ neoplasms (1.45, 1.06 to 2.00), and those of uncertain or unknown behaviour (1.32, 1.01 to 1.73). CONCLUSION: Overall cancer morbidity in Porton Down veterans was no different from that in non-Porton Down veterans.

K M Venables - One of the best experts on this subject based on the ideXlab platform.

  • p 2 01 epidemiological studies of the Porton Down veterans an update of cancer incidence and mortality to 2018
    Occupational and Environmental Medicine, 2019
    Co-Authors: Gemma Archer, Thomas Keegan, Claire Brooks, Lucy M Carpenter, K M Venables, Nicola T Fear
    Abstract:

    Introduction An update to the Porton Down Veterans Cohort study is planned for 2018–2021. Background Chemical warfare agents continue to be deployed by rogue states and terrorists, e.g. in Syria, Iraq, Tokyo, and Salisbury UK, yet their impact on long-term health is largely unknown. The Porton Down cohort comprises of 18 276 men who took part in the ‘human volunteer programme’ of chemical warfare agent research at Porton Down, UK, between 1941 to 1989, and a comparison group of 17 600 men who also served in the military. An original study linked veterans’ records to national registry data on cancer incidence and mortality up to 2004. By the end of 2004, 7306 of the Porton Down veterans and 6900 of the comparison cohort had died. The results showed Porton Down veterans had no overall excess of cancers (rate ratio (RR)=1.00, 95% CI 0.95–1.05) and a small (6%) excess of all-cause mortality (RR=1.06, 1.03–1.10) when compared with non-Porton Down veterans. Porton Down veterans had higher rates of certain cancers (e.g. ill-defined malignant neoplasms, and in situ neoplasms) and specific causes of death (e.g. genitourinary, circulatory and external causes). Objectives The updated study aims to replicate the original analyses but with an additional 15 years of follow-up – estimated to increase the number of deaths available for study to c 22 200. This will improve statistical power, allowing exposures and outcomes of interest from prior literature to be examined at a level of detail not possible in the original study, e.g. nerve agent antidotes, riot control agents, neurological mortality, and rarer cancers. Implications Greater understanding of the long-term risks associated with exposure to chemical agents could lead to raised awareness among policy makers and health care providers, leading to improved diagnosis and quality of care. Conflict of interest None

  • o5c 5 sarin exposures in a cohort of british military participants in human experimental research at Porton Down 1945 1987
    Occupational and Environmental Medicine, 2019
    Co-Authors: Thomas Keegan, Lucy M Carpenter, C Brooks, T Langdon, K M Venables
    Abstract:

    Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down, near Salisbury, is the UK’s centre for research on chemical warfare. Since WWI, a programme of experiments involving approximately 30 000 participants drawn from the UK armed services has been undertaken there. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data in a cohort of servicemen who attended Porton Down. Methods We have used existing data on exposures to UK servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans, all between 1945 and 1987. Of the 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For inhalation tests, assessed by changes in red blood cell cholinesterase median inhibition for was 41% (IQR 24%–51%), with a maximum of 87%. For dermal exposures, assessed by changes in unspecified cholinesterase, median inhibition was 22% (IQR 10%–37%), with a maximum inhibition of 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength f the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less apparent when protection was present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans. Acknowledgement We thank Nicola Fear and Gemma Archer, our collaborators in new work on these data, for their input.

  • sarin exposures in a cohort of british military participants in human experimental research at Porton Down 1945 1987
    Annals of Work Exposures and Health, 2018
    Co-Authors: Thomas Keegan, Lucy M Carpenter, C Brooks, T Langdon, K M Venables
    Abstract:

    Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK’s centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. Methods In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28–51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

  • dermal exposures to sarin in military veterans at Porton Down
    ISEE Conference Abstracts, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, T Langdon, S Walker, Lm Carpenter, K M Venables
    Abstract:

    Background The modification of dermal exposures by clothing, which may either protect from exposure or increase its effect, is of considerable interest. Here, we describe early analyses of the effects of dermal exposures to the nerve agent sarin, using data drawn from our previous cohort study of military veterans of chemical tests at Porton Down between, 1939-1989. Methods Data on exposures were abstracted from the Porton Down historical archive. For each nerve agent test we abstracted data on date and type of test, the principal chemical(s) used and exposure intensity, duration and route. We also noted the presence of exposure modifiers. Maximum percentage change in the following cholinesterase (ChE) measures were abstracted or calculated: unspecified, whole blood, plasma and/or red blood cell (RBC) ChE. Results 3597 veterans were recorded as involved in 4299 tests with nerve agents, 1945-1987. The most tested nerve agent was sarin: 2980 veterans were involved in 3511 tests. 288 sarin exposures were dermal (9.6%) and most of those were modified physically, eg by clothing (188; 65%). Dermal sarin tests took place 1951 - 1953. Quantity of exposure to dermal sarin was measured for 273 tests and ranged from 0.13 to 300 mg. Applied exposures were higher in tests with modification (IQR 200-300 mg with modification and 0.28-8 mg without). Change in ChE activity was available for 279 dermal sarin tests (97%). The median change was -22% (IQR -10 to - 37%, range +12.5 to -99%). The median without modification was -4.5% (IQR 0 to -13%) and -31% (IQR -19 to -46%) with modification. Conclusions The quantity of dermal exposure to sarin influenced effect. However, modifier use may be confounded by exposure so further investigation of the relationships between exposure, effect, and modification will be carried out.

  • assessment of exposure to sarin in military veterans at Porton Down
    Occupational and Environmental Medicine, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, Lucy M Carpenter, T Langdon, S Walker, K M Venables
    Abstract:

    Objectives Mortality and cancer incidence was recently examined in a cohort of >18 000 veterans of tests at Porton Down, 1941–89. Here we describe exposures to the nerve agent, sarin, and document the use of exposure or effect modifiers. Methods Data were abstracted from the Porton Down historical archive. Specific chemical names and the test dates were abstracted. For nerve agents information was also abstracted on modifiers (eg, respirators or protective chemicals). Pre-test and maximum change in cholinesterase (ChE) was calculated for unspecified, whole blood, plasma, and/or red blood cell (RBC) ChE. Results A total 3597 veterans were recorded in 4299 nerve agent tests 1945-87. Sarin was the most commonly-tested nerve agent (2980 veterans; 3511 tests). Most sarin tests were by the inhalation route (85%), 8% were dermal, 3% ocular. 53% of sarin tests were unprotected. Of the remainder, 30% involved physical protection (eg, respirator), 21% a chemical modifier (eg, pyridostigmine). Median exposure intensity was 12 mg.min/m 3 for unprotected inhalation tests (IQR 5.1–14.8 mg.min/m 3 ), 10.7 mg.min/m3 for tests with physical protection (IQR 7.4–13.9 mg.min/m 3 ). The median unprotected dermal exposure was 0.49 mg (IQR 0.2–8 mg) and 250 mg for protected dermal exposures (IQR 200–300 mg). Median RBC ChE activity decreased with increasing sarin exposure (n = 712 tests); this decrease was of a similar magnitude irrespective of protection status. Conclusions Sarin was the nerve agent most frequently tested on veterans at Porton Down. Availability of data on exposure intensity has allowed quantitative assessment of the effect of physical and chemical modifiers.

Claire Brooks - One of the best experts on this subject based on the ideXlab platform.

  • p 2 01 epidemiological studies of the Porton Down veterans an update of cancer incidence and mortality to 2018
    Occupational and Environmental Medicine, 2019
    Co-Authors: Gemma Archer, Thomas Keegan, Claire Brooks, Lucy M Carpenter, K M Venables, Nicola T Fear
    Abstract:

    Introduction An update to the Porton Down Veterans Cohort study is planned for 2018–2021. Background Chemical warfare agents continue to be deployed by rogue states and terrorists, e.g. in Syria, Iraq, Tokyo, and Salisbury UK, yet their impact on long-term health is largely unknown. The Porton Down cohort comprises of 18 276 men who took part in the ‘human volunteer programme’ of chemical warfare agent research at Porton Down, UK, between 1941 to 1989, and a comparison group of 17 600 men who also served in the military. An original study linked veterans’ records to national registry data on cancer incidence and mortality up to 2004. By the end of 2004, 7306 of the Porton Down veterans and 6900 of the comparison cohort had died. The results showed Porton Down veterans had no overall excess of cancers (rate ratio (RR)=1.00, 95% CI 0.95–1.05) and a small (6%) excess of all-cause mortality (RR=1.06, 1.03–1.10) when compared with non-Porton Down veterans. Porton Down veterans had higher rates of certain cancers (e.g. ill-defined malignant neoplasms, and in situ neoplasms) and specific causes of death (e.g. genitourinary, circulatory and external causes). Objectives The updated study aims to replicate the original analyses but with an additional 15 years of follow-up – estimated to increase the number of deaths available for study to c 22 200. This will improve statistical power, allowing exposures and outcomes of interest from prior literature to be examined at a level of detail not possible in the original study, e.g. nerve agent antidotes, riot control agents, neurological mortality, and rarer cancers. Implications Greater understanding of the long-term risks associated with exposure to chemical agents could lead to raised awareness among policy makers and health care providers, leading to improved diagnosis and quality of care. Conflict of interest None

  • dermal exposures to sarin in military veterans at Porton Down
    ISEE Conference Abstracts, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, T Langdon, S Walker, Lm Carpenter, K M Venables
    Abstract:

    Background The modification of dermal exposures by clothing, which may either protect from exposure or increase its effect, is of considerable interest. Here, we describe early analyses of the effects of dermal exposures to the nerve agent sarin, using data drawn from our previous cohort study of military veterans of chemical tests at Porton Down between, 1939-1989. Methods Data on exposures were abstracted from the Porton Down historical archive. For each nerve agent test we abstracted data on date and type of test, the principal chemical(s) used and exposure intensity, duration and route. We also noted the presence of exposure modifiers. Maximum percentage change in the following cholinesterase (ChE) measures were abstracted or calculated: unspecified, whole blood, plasma and/or red blood cell (RBC) ChE. Results 3597 veterans were recorded as involved in 4299 tests with nerve agents, 1945-1987. The most tested nerve agent was sarin: 2980 veterans were involved in 3511 tests. 288 sarin exposures were dermal (9.6%) and most of those were modified physically, eg by clothing (188; 65%). Dermal sarin tests took place 1951 - 1953. Quantity of exposure to dermal sarin was measured for 273 tests and ranged from 0.13 to 300 mg. Applied exposures were higher in tests with modification (IQR 200-300 mg with modification and 0.28-8 mg without). Change in ChE activity was available for 279 dermal sarin tests (97%). The median change was -22% (IQR -10 to - 37%, range +12.5 to -99%). The median without modification was -4.5% (IQR 0 to -13%) and -31% (IQR -19 to -46%) with modification. Conclusions The quantity of dermal exposure to sarin influenced effect. However, modifier use may be confounded by exposure so further investigation of the relationships between exposure, effect, and modification will be carried out.

  • assessment of exposure to sarin in military veterans at Porton Down
    Occupational and Environmental Medicine, 2011
    Co-Authors: Thomas Keegan, Claire Brooks, Lucy M Carpenter, T Langdon, S Walker, K M Venables
    Abstract:

    Objectives Mortality and cancer incidence was recently examined in a cohort of >18 000 veterans of tests at Porton Down, 1941–89. Here we describe exposures to the nerve agent, sarin, and document the use of exposure or effect modifiers. Methods Data were abstracted from the Porton Down historical archive. Specific chemical names and the test dates were abstracted. For nerve agents information was also abstracted on modifiers (eg, respirators or protective chemicals). Pre-test and maximum change in cholinesterase (ChE) was calculated for unspecified, whole blood, plasma, and/or red blood cell (RBC) ChE. Results A total 3597 veterans were recorded in 4299 nerve agent tests 1945-87. Sarin was the most commonly-tested nerve agent (2980 veterans; 3511 tests). Most sarin tests were by the inhalation route (85%), 8% were dermal, 3% ocular. 53% of sarin tests were unprotected. Of the remainder, 30% involved physical protection (eg, respirator), 21% a chemical modifier (eg, pyridostigmine). Median exposure intensity was 12 mg.min/m 3 for unprotected inhalation tests (IQR 5.1–14.8 mg.min/m 3 ), 10.7 mg.min/m3 for tests with physical protection (IQR 7.4–13.9 mg.min/m 3 ). The median unprotected dermal exposure was 0.49 mg (IQR 0.2–8 mg) and 250 mg for protected dermal exposures (IQR 200–300 mg). Median RBC ChE activity decreased with increasing sarin exposure (n = 712 tests); this decrease was of a similar magnitude irrespective of protection status. Conclusions Sarin was the nerve agent most frequently tested on veterans at Porton Down. Availability of data on exposure intensity has allowed quantitative assessment of the effect of physical and chemical modifiers.

  • mortality and cancer morbidity in a cohort of british military veterans included in chemical warfare agent experiments at Porton Down
    Journal of Epidemiology and Community Health, 2009
    Co-Authors: Lm Carpenter, Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, T Langdon, K M Venables, L Linsell, Mark J Nieuwenhuijsen
    Abstract:

    To study whether there may be long-term effects on the mortality and cancer morbidity of participants in experimental research related to chemical warfare agents conducted at the UK research facility at Porton Down. Historical cohort study. 18 276 male members of the UK armed forces who spent one or more short periods at Porton Down between 1941 and 1989 and a comparison group of 17 600 non-Porton Down veterans followed to 31 December, 2004. All veterans were considered for the cancer analyses, excluding those …

  • mortality in british military participants in human experimental research into chemical warfare agents at Porton Down cohort study
    BMJ, 2009
    Co-Authors: K M Venables, Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, Mark J Nieuwenhuijsen, T Langdon, L Linsell, V Beral
    Abstract:

    Objective To investigate any long term effects on mortality in participants in experimental research related to chemical warfare agents from 1941 to 1989. Design Historical cohort study. Data sources Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. Participants 18 276 male members of the UK armed forces who had spent one or more short periods (median 4 days between first and last test) at Porton Down and a comparison group of 17 600 non-Porton Down veterans followed to 31 December 2004. Main outcome measures Mortality rate ratio of Porton Down compared with non-Porton Down veterans and standardised mortality ratio of each veteran group compared with the general population. Both ratios adjusted for age group and calendar period. Results Porton Down veterans were similar to non-Porton Down veterans in year of enlistment (median 1951) but had longer military service (median 6.2 v 5.0 years). After a median follow-up of 43 years, 40% (7306) of Porton Down and 39% (6900) of non-Porton Down veterans had died. All cause mortality was slightly greater in Porton Down veterans (rate ratio 1.06, 95% confidence interval 1.03 to 1.10, P<0.001), more so for deaths outside the UK (1.26, 1.09 to 1.46). Of 12 cause specific groups examined, rate ratios in Porton Down veterans were increased for deaths attributed to infectious and parasitic (1.57, 1.07 to 2.29), genitourinary (1.46, 1.04 to 2.04), circulatory (1.07, 1.01 to 1.12), and external (non-medical) (1.17, 1.00 to 1.37) causes and decreased for deaths attributed to in situ, benign, and unspecified neoplasms (0.60, 0.37 to 0.99). There was no clear relation between type of chemical exposure and cause specific mortality. The mortality in both groups of veterans was lower than that in the general population (standardised mortality ratio 0.88, 0.85 to 0.90; 0.82, 0.80 to 0.84). Conclusions Mortality was slightly higher in Porton Down than non-Porton Down veterans. With lack of information on other important factors, such as smoking or service overseas, it is not possible to attribute the small excess mortality to chemical exposures at Porton Down.

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  • mortality and cancer morbidity in a cohort of british military veterans included in chemical warfare agent experiments at Porton Down
    Journal of Epidemiology and Community Health, 2009
    Co-Authors: Lm Carpenter, Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, T Langdon, K M Venables, L Linsell, Mark J Nieuwenhuijsen
    Abstract:

    To study whether there may be long-term effects on the mortality and cancer morbidity of participants in experimental research related to chemical warfare agents conducted at the UK research facility at Porton Down. Historical cohort study. 18 276 male members of the UK armed forces who spent one or more short periods at Porton Down between 1941 and 1989 and a comparison group of 17 600 non-Porton Down veterans followed to 31 December, 2004. All veterans were considered for the cancer analyses, excluding those …

  • mortality in british military participants in human experimental research into chemical warfare agents at Porton Down cohort study
    BMJ, 2009
    Co-Authors: K M Venables, Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, Mark J Nieuwenhuijsen, T Langdon, L Linsell, V Beral
    Abstract:

    Objective To investigate any long term effects on mortality in participants in experimental research related to chemical warfare agents from 1941 to 1989. Design Historical cohort study. Data sources Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. Participants 18 276 male members of the UK armed forces who had spent one or more short periods (median 4 days between first and last test) at Porton Down and a comparison group of 17 600 non-Porton Down veterans followed to 31 December 2004. Main outcome measures Mortality rate ratio of Porton Down compared with non-Porton Down veterans and standardised mortality ratio of each veteran group compared with the general population. Both ratios adjusted for age group and calendar period. Results Porton Down veterans were similar to non-Porton Down veterans in year of enlistment (median 1951) but had longer military service (median 6.2 v 5.0 years). After a median follow-up of 43 years, 40% (7306) of Porton Down and 39% (6900) of non-Porton Down veterans had died. All cause mortality was slightly greater in Porton Down veterans (rate ratio 1.06, 95% confidence interval 1.03 to 1.10, P<0.001), more so for deaths outside the UK (1.26, 1.09 to 1.46). Of 12 cause specific groups examined, rate ratios in Porton Down veterans were increased for deaths attributed to infectious and parasitic (1.57, 1.07 to 2.29), genitourinary (1.46, 1.04 to 2.04), circulatory (1.07, 1.01 to 1.12), and external (non-medical) (1.17, 1.00 to 1.37) causes and decreased for deaths attributed to in situ, benign, and unspecified neoplasms (0.60, 0.37 to 0.99). There was no clear relation between type of chemical exposure and cause specific mortality. The mortality in both groups of veterans was lower than that in the general population (standardised mortality ratio 0.88, 0.85 to 0.90; 0.82, 0.80 to 0.84). Conclusions Mortality was slightly higher in Porton Down than non-Porton Down veterans. With lack of information on other important factors, such as smoking or service overseas, it is not possible to attribute the small excess mortality to chemical exposures at Porton Down.

  • cancer morbidity in british military veterans included in chemical warfare agent experiments at Porton Down cohort study
    BMJ, 2009
    Co-Authors: Lucy M Carpenter, Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, Mark J Nieuwenhuijsen, T Langdon, L Linsell, V Beral
    Abstract:

    OBJECTIVE: To determine cancer morbidity in members of the armed forces who took part in tests of chemical warfare agents from 1941 to 1989. DESIGN: Historical cohort study, with cohort members followed up to December 2004. DATA SOURCE: Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. PARTICIPANTS: All veterans included in the cohort study of mortality, excluding those known to have died or been lost to follow-up before 1 January 1971 when the UK cancer registration system commenced: 17,013 male members of the UK armed forces who took part in tests (Porton Down veterans) and a similar group of 16,520 men who did not (non-Porton Down veterans). MAIN OUTCOME MEASURES: Cancer morbidity in each group of veterans; rate ratios, with 95% confidence intervals, adjusted for age group and calendar period. RESULTS: 3457 cancers were reported in the Porton Down veterans compared with 3380 cancers in the non-Porton Down veterans. While overall cancer morbidity was the same in both groups (rate ratio 1.00, 95% confidence interval 0.95 to 1.05), Porton Down veterans had higher rates of ill defined malignant neoplasms (1.12, 1.02 to 1.22), in situ neoplasms (1.45, 1.06 to 2.00), and those of uncertain or unknown behaviour (1.32, 1.01 to 1.73). CONCLUSION: Overall cancer morbidity in Porton Down veterans was no different from that in non-Porton Down veterans.

  • exposures recorded for participants in the uk chemical warfare agent human research programme 1941 1989
    Annals of Occupational Hygiene, 2009
    Co-Authors: Thomas Keegan, Tony Fletcher, Claire Brooks, Pat Doyle, Noreen Maconochie, Mark J Nieuwenhuijsen, T Langdon, S Walker, L Linsell, Lucy M Carpenter
    Abstract:

    Objectives: This study describes exposures to military veterans who participated between 1941 and 1989 in British research at Porton Down on the effects of exposure to chemical warfare agents and to defences against those agents. The study is part of a programme of epidemiological research initiated in response to service veterans' concerns about possible long-term health effects of their participation. Methods: All entries in 97 books held in the Porton Down historical experimental archive covering the years 1939-1989 were reviewed. For tests between April 1941 and December 1989, data were abstracted on chemicals used, with additional detail abstracted for tests involving vesicants and nerve agents. For tests recorded during 1939-1941, similar data were abstracted for a representative sample of tests. Results: Historical data were abstracted for 17 303 veterans included in the cohort study of 18 276 servicemen who took part in tests at Porton Down between 1941 and 1989. The median number of days per veteran on which tests were carried out was 2 days. The median difference between the last and first day of testing was 4 days. A large number of chemicals were tested over this period (n = 492). The type of chemical tested varied over time. Exposures were often modified by respirator use or use of protective clothing or protective equipment. It was possible to assign a quantitative measure of cumulative exposure to 73% of veterans exposed to the vesicant sulphur mustard-025EF3491 (34%) of exposed veterans had cumulative exposures >= 10.63 mg and for 70% of veterans exposed to the nerve agent sarin-025EF658 (29%) of exposed veterans had cumulative exposures >= 15.0 mg min m(-3). Ninety-three per cent of veterans exposed to sulphur mustard were classified to a semi-quantitative scale of dermal effect-025EF3771 (37%) had a vesicle or necrosed area, and 69% of veterans exposed to sarin could be categorized by change in blood cholinesterase activity-025EF1033 (31%) had a depression in cholinesterase activity of >= 30%. Conclusions: The experimental archive at Porton Down has proved to be a rich source of data on tests conducted between 1941 and 1989. It has been possible to categorize most veterans according to date of test, chemical group, chemical, type of protection and, for certain chemicals, level of exposure and/or degree of acute toxicity. These categorizations have been used to assign veterans to exposure groups for epidemiological analysis.

  • Exposures recorded for participants in the UK Chemical Warfare Agent Human Research Programme, 1941-1989.
    'Oxford University Press (OUP)', 2009
    Co-Authors: Tj Keegan, Mark J Nieuwenhuijsen, Walker Sas, Brooks C, Langdon T, Linsell L, Maconochie Nes, Doyle P, Fletcher T, Lm Carpenter
    Abstract:

    OBJECTIVES: This study describes exposures to military veterans who participated between 1941 and 1989 in British research at Porton Down on the effects of exposure to chemical warfare agents and to defences against those agents. The study is part of a programme of epidemiological research initiated in response to service veterans' concerns about possible long-term health effects of their participation. METHODS: All entries in 97 books held in the Porton Down historical experimental archive covering the years 1939-1989 were reviewed. For tests between April 1941 and December 1989, data were abstracted on chemicals used, with additional detail abstracted for tests involving vesicants and nerve agents. For tests recorded during 1939-1941, similar data were abstracted for a representative sample of tests. RESULTS: Historical data were abstracted for 17 303 veterans included in the cohort study of 18,276 servicemen who took part in tests at Porton Down between 1941 and 1989. The median number of days per veteran on which tests were carried out was 2 days. The median difference between the last and first day of testing was 4 days. A large number of chemicals were tested over this period (n = 492). The type of chemical tested varied over time. Exposures were often modified by respirator use or use of protective clothing or protective equipment. It was possible to assign a quantitative measure of cumulative exposure to 73% of veterans exposed to the vesicant sulphur mustard--3491 (34%) of exposed veterans had cumulative exposures > or =10.63 mg and for 70% of veterans exposed to the nerve agent sarin--658 (29%) of exposed veterans had cumulative exposures > or =15.0 mg min m(-3). Ninety-three per cent of veterans exposed to sulphur mustard were classified to a semi-quantitative scale of dermal effect--3771 (37%) had a vesicle or necrosed area, and 69% of veterans exposed to sarin could be categorized by change in blood cholinesterase activity--1033 (31%) had a depression in cholinesterase activity of > or =30%. CONCLUSIONS: The experimental archive at Porton Down has proved to be a rich source of data on tests conducted between 1941 and 1989. It has been possible to categorize most veterans according to date of test, chemical group, chemical, type of protection and, for certain chemicals, level of exposure and/or degree of acute toxicity. These categorizations have been used to assign veterans to exposure groups for epidemiological analysis