38 results on '"Frank M, Sullivan"'
Search Results
2. Determinants of motivation to quit in smokers screened for the early detection of lung cancer: a qualitative study
- Author
-
Ben Young, Kavita Vedhara, Denise Kendrick, Roberta Littleford, John F. R. Robertson, Frank M. Sullivan, Stuart Schembri, Roshan das Nair, and in collaboration with the ECLS study team
- Subjects
Smoking cessation ,Early cancer detection ,Lung cancer ,Teachable moment ,Thematic analysis ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background The promotion of smoking cessation within lung cancer screening could lead to benefits for smoking-related disease and improve cost-effectiveness of screening. Little is known about how smokers respond to lung cancer screening and how this impacts smoking behaviour. We aimed to understand how lung cancer screening influences individual motivations about smoking, including in those who have stopped smoking since screening. Methods Thirty one long-term smokers aged 51–74 took part in semi-structured interviews about smoking. They had been screened with the EarlyCDT-Lung Test (13 positive result; 18 negative) as part of the Early Cancer Detection Test Lung Cancer Scotland Study. They were purposively sampled for interview based on their self-reported post-screening smoking behaviour. Eleven participants had stopped smoking since screening. Verbatim interview transcripts were analysed using thematic analysis. Results Two key overarching themes were interpretations of screening test results and emotional responses to those interpretations. Participants’ understanding of the risk implied by their test result was often inaccurate, for example a negative result interpreted as an ‘all-clear’ from lung cancer and a positive result as meaning lung cancer would definitely develop. Those interpretations led to emotional responses (fear, shock, worry, relief, indifference) influencing motivations about smoking. Other themes included a wake-up call causing changes in perceived risk of smoking-related disease, a feeling that now is the time to stop smoking and family influences. There was no clear pattern in smoking motivations in those who received positive or negative test results. Of those who had stopped smoking, some cited screening experiences as the sole motivation, some cited screening along with other coinciding factors, and others cited non-screening reasons. Cues to change were experienced at different stages of the screening process. Some participants indicated they underwent screening to try and stop smoking, while others expressed little or no desire to stop. Conclusions We observed complex and individualised motivations about smoking following lung cancer screening. To be most effective, smoking cessation support in this context should explore understanding of screening test results and may need to be highly tailored to individual emotional responses to screening.
- Published
- 2018
- Full Text
- View/download PDF
3. Recording COVID-19 consultations: review of symptoms, risk factors, and proposed SNOMED CT terms
- Author
-
Bhautesh Dinesh Jani, Jill P Pell, Dylan McGagh, Harshana Liyanage, Dave Kelly, Simon de Lusignan, Christopher J Weatherburn, Ronnie Burns, Frank M Sullivan, and Frances S Mair
- Subjects
covid-19 ,systematised nomenclature of medicine ,general practice ,primary health care ,medical records systems, computerised ,Medicine (General) ,R5-920 - Abstract
Background: There is an urgent need for epidemiological research in primary care to develop risk assessment processes for patients presenting with COVID-19, but lack of a standardised approach to data collection is a significant barrier to implementation. Aim: To collate a list of relevant symptoms, assessment items, demographics, and lifestyle and health conditions associated with COVID-19, and match these data items with corresponding SNOMED CT clinical terms to support the development and implementation of consultation templates. Design & setting: Published and preprint literature for systematic reviews, meta-analyses, and clinical guidelines describing the symptoms, assessment items, demographics, and/or lifestyle and health conditions associated with COVID-19 and its complications were reviewed. Corresponding clinical concepts from SNOMED CT, a widely used structured clinical vocabulary for electronic primary care health records, were identified. Method: Guidelines and published and unpublished reviews (N = 61) were utilised to collate a list of relevant data items for COVID-19 consultations. The NHS Digital SNOMED CT Browser was used to identify concept and descriptive identifiers. Key implementation challenges were conceptualised through a Normalisation Process Theory (NPT) lens. Results: In total, 32 symptoms, eight demographic and lifestyle features, 25 health conditions, and 20 assessment items relevant to COVID-19 were identified, with proposed corresponding SNOMED CT concepts. These data items can be adapted into a consultation template for COVID-19. Key implementation challenges include: 1) engaging with key stakeholders to achieve ’buy in’; and 2) ensuring any template is usable within practice settings. Conclusion: Consultation templates for COVID-19 are needed to standardise data collection, facilitate research and learning, and potentially improve quality of care for COVID-19.
- Published
- 2020
- Full Text
- View/download PDF
4. Efficient identification of patients eligible for clinical studies using case-based reasoning on Scottish Health Research register (SHARE).
- Author
-
Wen Shi, Tom Kelsey, and Frank M. Sullivan
- Published
- 2020
- Full Text
- View/download PDF
5. A secure electronic diary and data collection tool.
- Author
-
Kenny Morrison, Ian W. Ricketts, Martyn C. Jones, Derek W. Johnston, Nigel B. Pitts, and Frank M. Sullivan
- Published
- 2009
- Full Text
- View/download PDF
6. Assessment of background levels of autoantibodies as a prognostic marker for severe SARS-CoV-2 infection
- Author
-
Frank M. Sullivan, Agnes Tello, Petra Rauchhaus, Virginia Hernandez Santiago, Fergus Daly, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Population and Behavioural Science Division, and University of St Andrews. School of Medicine
- Subjects
Current or ex-smokers ,SDG 3 - Good Health and Well-being ,Mortality prediction ,Biochemistry (medical) ,Clinical Biochemistry ,QR180 ,COVID-19 ,QR180 Immunology ,3rd-DAS ,Serum biomarkers ,Lung cancer ,respiratory tract diseases - Abstract
This project was funded by The Lung Foundation. Background : Patients with more severe forms of SARS-CoV-2 exhibit activation of immunological cascades. Participants (current or ex-smokers with at least 20 years pack history) in a trial (Early Diagnosis of Lung Cancer, Scotland [ECLS]) of autoantibody detection to predict lung cancer risk had seven autoantibodies measured 5 years before the pandemic. This study compared the response to Covid infection in study participants who tested positive and negative to antibodies to tumour-associated antigens: p53, NY-ESO-1, CAGE, GBU4-5, HuD, MAGE A4 and SOX2. Methods : Autoantibody data from the ECLS study was deterministically linked to the EAVE II database, a national, real-time prospective cohort using Scotland’s health data infrastructure, to describe the epidemiology of SARS-CoV-2 infection, patterns of healthcare use and outcomes. The strength of associations was explored using a network algorithm for exact contingency table significance testing by permutation. Results : There were no significant differences discerned between SARS-CoV-2 test results and EarlyCDT-Lung test results (p = 0.734). An additional analysis of intensive care unit (ICU) admissions detected no significant differences between those who tested positive and negative. Subgroup analyses showed no difference in COVID-19 positivity or death rates amongst those diagnosed with chronic obstructive pulmonary disease (COPD) with positive and negative EarlyCDT results. Conclusions : This hypothesis-generating study demonstrated no clinically valuable or statistically significant associations between EarlyCDT positivity in 2013-15 and the likelihood of SARS-CoV-2 positivity in 2020, ICU admission or death in all participants (current or ex-smokers with at least 20 years pack history) or in those with COPD or lung cancer. Publisher PDF
- Published
- 2022
7. Using electronic patient records to inform strategic decision making in primary care.
- Author
-
Elizabeth Mitchell, Frank M. Sullivan, Graham Watt, Jeremy M. Grimshaw, and Peter T. Donnan
- Published
- 2004
- Full Text
- View/download PDF
8. Viewpoint Paper: e-Prescribing, Efficiency, Quality: Lessons from the Computerization of UK Family Practice.
- Author
-
Charles P. Schade, Frank M. Sullivan, Simon de Lusignan, and Jean Madeley
- Published
- 2006
- Full Text
- View/download PDF
9. Whole population secondary prevention of Coronary Heart Disease in Scotland: The HEARTS database.
- Author
-
Frank M. Sullivan, Peter T. Donnan, and Tom Love
- Published
- 2004
- Full Text
- View/download PDF
10. A Validated Logistic Regression Model to Identify Coronary Heart Disease patients (CHD) within Primary Care Databases in the United Kingdom.
- Author
-
Krish Thiru, Peter T. Donnan, and Frank M. Sullivan
- Published
- 2003
11. Extending Proof of Concept from DARTS to HEARTS.
- Author
-
Hamish Dougall, Neill McEwan, Douglas Boyle, Andrew D. Morris, and Frank M. Sullivan
- Published
- 2001
12. The utility of liver function tests for mortality prediction within one year in primary care using the algorithm for liver function investigations (ALFI).
- Author
-
David J McLernon, John F Dillon, Frank M Sullivan, Paul Roderick, William M Rosenberg, Stephen D Ryder, and Peter T Donnan
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. METHODS: In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices. RESULTS: From the derivation cohort (n = 95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n = 11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. CONCLUSIONS: The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV.
- Published
- 2012
- Full Text
- View/download PDF
13. A managed clinical network for cardiac services: set-up, operation and impact on patient care
- Author
-
Karen E. Hamilton, Frank M. Sullivan, Peter T. Donnan, Rex Taylor, Divine Ikenwilo, Anthony Scott, Chris Baker, and Sally Wyke
- Subjects
clinical networks ,disease management ,integrated healthcare networks ,managed care ,Medicine (General) ,R5-920 - Abstract
Purpose: To investigate the set up and operation of a Managed Clinical Network for cardiac services and assess its impact on patient care. Methods: This single case study used process evaluation with observational before and after comparison of indicators of quality of care and costs. The study was conducted in Dumfries and Galloway, Scotland and used a three-level framework. Process evaluation of the network set-up and operation through a documentary review of minutes; guidelines and protocols; transcripts of fourteen semi-structured interviews with health service personnel including senior managers, general practitioners, nurses, cardiologists and members of the public. Outcome evaluation of the impact of the network through interrupted time series analysis of clinical data of 202 patients aged less than 76 years admitted to hospital with a confirmed myocardial infarction one-year pre and one-year post, the establishment of the network. The main outcome measures were differences between indicators of quality of care targeted by network protocols. Economic evaluation of the transaction costs of the set-up and operation of the network and the resource costs of the clinical care of the 202 myocardial infarction patients from the time of hospital admission to 6 months post discharge through interrupted time series analysis. The outcome measure was different in National Health Service resource use. Results: Despite early difficulties, the network was successful in bringing together clinicians, patients and managers to redesign services, exhibiting most features of good network management. The role of the energetic lead clinician was crucial, but the network took time to develop and ‘bed down’. Its primary “modus operand” was the development of a myocardial infarction pathway and associated protocols. Of sixteen clinical care indicators, two improved significantly following the launch of the network and nine showed improvements, which were not statistically significant. There was no difference in resource use. Discussion and conclusions: The Managed Clinical Network made a difference to ways of working, particularly in breaching traditional boundaries and involving the public, and made modest changes in patient care. However, it required a two-year “set-up” period. Managed clinical networks are complex initiatives with an increasing profile in health care policy. This study suggests that they require energetic leadership and improvements are likely to be slow and incremental.
- Published
- 2005
14. A two-generation reproductive toxicity study of sodium molybdate dihydrate administered in drinking water or diet to Sprague-Dawley rats
- Author
-
Frank M. Sullivan, Sue A. Hubbard, Sandra Carey, Alan M. Hoberman, and F. Jay Murray
- Subjects
Litter (animal) ,Male ,010501 environmental sciences ,Biology ,Toxicology ,Sodium Molybdate Dihydrate ,01 natural sciences ,Rats, Sprague-Dawley ,03 medical and health sciences ,Eating ,Animal science ,Pregnancy ,Sprague dawley rats ,Animals ,Adverse effect ,030304 developmental biology ,0105 earth and related environmental sciences ,Estrous cycle ,Molybdenum ,0303 health sciences ,No-Observed-Adverse-Effect Level ,Reproductive Physiological Phenomena ,Drinking Water ,Body Weight ,Sperm ,Diet ,Gestation ,Female ,Reproductive toxicity - Abstract
In an OECD Test Guideline 416 multigenerational study, groups of 24 male and 24 female Sprague-Dawley rats were administered sodium molybdate dihydrate at 0, 5, 17, or 40 mg molybdenum (Mo)/kg bw/day in the drinking water or 40 mg Mo/kg bw/day in the diet over two generations to assess reproductive toxicity. No adverse effect on reproductive function was observed at any dose level in either generation as indicated by no significant dose-related effect on estrus cycles, sperm parameters, mating, fertility, gestation, litter size, pup survival, growth or postnatal development. Systemic toxicity, including decreased body weight, food consumption (males only) and water consumption, was observed among both sexes given 40 mg Mo/kg bw/day in the diet. Serum levels of Mo and copper were increased in a dose-related manner. The No Observed Adverse Effect Levels (NOAEL) are 17 mg Mo/kg bw/day for systemic toxicity and 40 mg Mo/kg bw/day for reproductive toxicity.
- Published
- 2018
15. An overview of male reproductive studies of boron with an emphasis on studies of highly exposed Chinese workers
- Author
-
Yanhong Li, Frank M. Sullivan, Irene Brüske-Hohlfeld, B. Dwight Culver, Anthony R. Scialli, and Jens Peter Bonde
- Subjects
Male ,inorganic chemicals ,China ,media_common.quotation_subject ,Physiology ,Semen ,Fertility ,Semen analysis ,Toxicology ,Mice ,Dogs ,Pregnancy ,Occupational Exposure ,Testis ,medicine ,Animals ,Humans ,Sex Ratio ,Boron ,media_common ,Sperm Count ,medicine.diagnostic_test ,business.industry ,Reproduction ,medicine.disease ,Spermatozoa ,Sperm ,Rats ,Toxicity ,Female ,business ,Water Pollutants, Chemical ,Sex ratio - Abstract
Boron treatment of rats, mice, and dogs has been associated with testicular toxicity, characterized by inhibited spermiation at lower dose levels and a reduction in epididymal sperm count at higher dose levels. The no-adverse-effect level for reproductive effects in male rats is 17.5mg B/kg bw/day. Earlier studies in human workers and populations have not identified adverse effects of boron exposure on fertility, but outcome measures in these studies were relatively insensitive, based mainly on family size and did not include an evaluation of semen end points. A recent study of nearly 1000 men working in boron (B) mining or processing in Liaoning province in northeast China has been published in several Chinese and a few English language papers. This study included individual assessment of boron exposure, interview data on reproductive experience and semen analysis. Employed men living in the same community and in a remote community were used as controls. Boron workers (n=75) had a mean daily boron intake of 31.3mg B/day, and a subset of 16 of these men, employed at a plant where there was heavy boron contamination of the water supply, had an estimated mean daily boron intake of 125 mg B/day. Estimates of mean daily boron intake in local community and remote background controls were 4.25mg B/day and 1.40 mg/day, respectively. Reproductive outcomes in the wives of 945 boron workers were not significantly different from outcomes in the wives of 249 background control men after adjustment for potential confounders. There were no statistically significant differences in semen characteristics between exposure groups, including in the highly exposed subset, except that sperm Y:X ratio was reduced in boron workers. Within exposure groups the Y:X ratio did not correlate with the boron concentration in blood, semen and urine. In conclusion, while boron has been shown to adversely affect male reproduction in laboratory animals, there is no clear evidence of male reproductive effects attributable to boron in studies of highly exposed workers.
- Published
- 2010
16. List of Contributors
- Author
-
Mark Anderson, Susan M. Barlow, Matitiahu Berkovitch, Cornelia Borisch, Christina D. Chambers, Maurizio Clementi, Benedikte-Noël Cuppers, Maria Ellfolk, Jan M. Friedman, Lee H. Goldstein, Juliane Habermann, Henry M. Hess, Stefanie Hultzsch, Eleanor Hüttel, Angela Kayser, Gudula Kirtschig, Ruth A. Lawrence, Fernanda Sales luiz Vianna, Heli Malm, Paul Merlob, Richard K. Miller, Marc Oppermann, Asher Ornoy, Stephanie Padberg, Mary Panse, Paul Peters, Janine E. Polifka, Christof Schaefer, Lavinia Schüler-Faccini, Sally Stephens, Frank M. Sullivan, Gerard H.A. Visser, Corinna Weber-SchÖendorfer, Bernke Te Winkel, Katherine L. Wisner, and Laura M. Yates
- Published
- 2015
17. Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats
- Author
-
Frank M. Sullivan, Rochelle W. Tyl, Sandra Carey, F. Jay Murray, and Asheesh K. Tiwary
- Subjects
medicine.medical_specialty ,Developmental toxicity ,Molybdate ,Toxicology ,Fetal Development ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Fetus ,Pregnancy ,Internal medicine ,medicine ,Sprague dawley rats ,Animals ,Developmental ,Adverse effect ,chemistry.chemical_classification ,Molybdenum ,Oxidase test ,Toxicity ,Dose-Response Relationship, Drug ,business.industry ,Abnormalities, Drug-Induced ,Diet ,Rats ,Endocrinology ,chemistry ,Fetal Weight ,Dietary Supplements ,Female ,Essential nutrient ,business ,Copper - Abstract
Molybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2 μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain. In the current study the developmental toxicity of sodium molybdate dihydrate as a representative of a broad class of soluble molybdenum(VI) compounds, was given in the diet to Sprague Dawley rats in accordance with OECD Test Guideline 414. Dose levels of 0, 3, 10, 20 and 40 mg Mo/kg bw/day were administered from GD6 to GD20. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL observed in this study was 40 mg Mo/kg bw/day, the highest dose tested.
- Published
- 2014
18. Summary of research needs
- Author
-
B. Dwight Culver and Frank M. Sullivan
- Subjects
business.industry ,Endocrinology, Diabetes and Metabolism ,Reproduction (economics) ,media_common.quotation_subject ,Biochemistry (medical) ,Clinical Biochemistry ,Nanotechnology ,General Medicine ,Research needs ,Biochemistry ,Inorganic Chemistry ,Human health ,Need to know ,Medicine ,Engineering ethics ,Element (criminal law) ,business ,Skepticism ,media_common - Abstract
A symposium such as this shows how much we know about this element, boron, and also how little we know. Sufficient evidence has been presented to convince some attendees that boron is essential for successful reproduction in some species. Others exhibit healthy skepticism and want further convincing. Most importantly, we need to know if boron is essential for human health and well-being, and if so, how much is required. Much has been accomplished by the extremely generous collaboration between individual researchers in this field of boron research, and there is still room for many more collaborators to join in this exciting search. A review of the articles presented will identify quickly fruitful areas for future research.
- Published
- 1998
19. Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the teratology information service
- Author
-
Frank M. Sullivan, Glyn Volans, and Patricia R. McElhatton
- Subjects
medicine.medical_specialty ,Poison Control Centers ,medicine.medical_treatment ,Toxicology ,Drug overdose ,Acetylcysteine ,Embryonic and Fetal Development ,Pregnancy ,London ,medicine ,Humans ,Referral and Consultation ,Acetaminophen ,business.industry ,Obstetrics ,Pregnancy Outcome ,Gestational age ,medicine.disease ,Gastric lavage ,Teratology ,Teratogens ,Prenatal Exposure Delayed Effects ,Drug Information Services ,Gestation ,Female ,Drug Overdose ,business ,Follow-Up Studies ,medicine.drug - Abstract
A prospective study was carried out to investigate the outcome of pregnancy in 300 women who had self-administered an overdose of paracetamol, either alone, or as part of a combined preparation. Exposure occurred in all trimesters. The most striking feature of this study is that the majority of the pregnancies had normal outcomes. Over half of the mothers (160 = 53%) required treatment for the overdose, and 49 of these had specific antidotes (33 mothers had acetylcysteine and 16 mothers had methionine). The rest of the mothers were given nonspecific treatments including ipecacuanha (52), gastric lavage (42), and charcoal (16). None of the mothers died. There were 219 liveborn infants with no malformations, 61 of whom had been exposed in the first trimester. Eleven liveborn infants had malformations; none was exposed in the first trimester. On other infant exposed at 18 weeks had a diaphragmatic hernia; this pregnancy was terminated at 22 weeks. In none of these 12 infants can the malformations be directly associated with paracetamol exposure. There were no apparent differences either in the sex ratio or the body weights of term infants. There were seven full-term infants with neonatal problems that seem unrelated to paracetamol exposure. Six premature infants also had neonatal problems, which were more likely to be related to their degree of prematurity rather than paracetamol exposure. There was no obvious relationship between the time of exposure and the time of delivery. The overall conclusion is that paracetamol overdose per se is not an indication for termination of pregnancy.
- Published
- 1997
20. 90-Day subchronic toxicity study of sodium molybdate dihydrate in rats
- Author
-
Frank M. Sullivan, Sandra Carey, F. Jay Murray, and Asheesh K. Tiwary
- Subjects
Serum ,Male ,medicine.medical_specialty ,chemistry.chemical_element ,Estrous Cycle ,Molybdate ,Toxicology ,Kidney ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Estrus ,Internal medicine ,medicine ,Animals ,Genitalia ,Adverse effect ,Estrous cycle ,Molybdenum ,No-Observed-Adverse-Effect Level ,Toxicity ,Sperm Count ,Body Weight ,Toxicity Tests, Subchronic ,General Medicine ,Sperm ,Diet ,Rats ,Endocrinology ,chemistry ,Liver ,Histopathology ,Female ,Selenium ,Copper - Abstract
This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague–Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day. No treatment-related adverse effects on reproductive organ weights or histopathology, estrus cycles or sperm parameters were observed at any dose level. No adverse effects were observed in the high dose animals after the 60-day recovery period, with the exception that male rats did not fully recover from reduced body weight. Serum blood, liver and kidney samples were analyzed for molybdenum, copper, zinc, manganese, iron, cobalt and selenium; high levels of molybdenum and copper were found in the serum, blood, liver and kidneys of rats treated with 60mgMo/kgbw/day. In conclusion, the LOAEL and NOAEL for molybdenum were determined to be 60 and 17mgMo/kgbw/day, respectively.
- Published
- 2013
21. Toxicological effects of inorganic boron compounds in animals: A review of the literature
- Author
-
Frank M. Sullivan and Susan A. Hubbard
- Subjects
education.field_of_study ,Borax ,Population ,Developmental toxicity ,Physiology ,chemistry.chemical_element ,Micronutrient ,Biochemistry ,Acute toxicity ,Boric acid ,Toxicology ,chemistry.chemical_compound ,chemistry ,Toxicity ,education ,Boron - Abstract
Boron is a ubiquitous element found widely distributed in the environment and is a normal component of a healthy diet. It is an essential micronutrient for plants, and there is evidence to suggest that boron is of nutritional importance, if not essential, for humans. The majority of toxicological studies have been reported on boric acid or borax. The inorganic borates display low acute toxicity. They are either not irritant or mild skin and eye irritants. They are not skin sensitisers, nor are they mutagenic or carcinogenic. The most sensitive endpoints of toxicity are considered to be effects on the reproductive organs, fertility in males, and developmental effects. The doses that cause these effects are far higher than any levels to which the human population could be exposed. The NOAELs from a rat developmental study (for a reduction on fetal weight) and from a fertility study considered to be the most appropriate for risk assessment were 9.6 mg B/kg bw/day and 17.5 mg B/kg bw/day, respectively. Man would need to consume daily some 3.3 g of boric acid (or 5.0 g borax) to ingest the same dose level as the lowest animal NOAEL. Sodium perborate tetrahydrate did not display the same response as boric acid or borax in that no adverse effects were seen in the testis, and developmental effects were only seen at doses causing maternal toxicity. This indicates the need to consider the toxicity of certain borate salts individually and to assess their risks separately. © 1997 Wiley-Liss, Inc.
- Published
- 1996
22. Regulatory and political perspectives in reproductive and developmental hazard assessment
- Author
-
Frank M. Sullivan
- Subjects
Actuarial science ,Process (engineering) ,Reproduction ,Legislation ,General Medicine ,Hazard analysis ,Toxicology ,Risk Assessment ,Hazard ,Scientific evidence ,Fertility ,Fetus ,Work (electrical) ,Pregnancy ,Environmental protection ,Political science ,Animals ,Humans ,Female ,Risk assessment ,Health policy - Abstract
The World Health Organisation is attempting to harmonise the processes of risk assessment worldwide in the hope that assessments performed in one country will be acceptable to other countries. This would reduce not only duplication of work by scientists, but would also reduce to a minimum the need for animal studies. There are differences in the scientific approaches used in different countries to the process of hazard and risk assessment. For example, in the USA risk assessment is focusing on development of mathematical models to describe dose-response relationships to define, for example, a benchmark dose. In Europe much less use is made of such models. More dependence is placed on no-effect levels, and the use of safety factors is much more highly developed. Political considerations come into play when one looks at the use, or misuse, that may be made of such hazard and risk assessments. Once a chemical has been classified and placed on a 'list' of reprotoxic chemicals, the underlying criteria may be ignored and actions taken which are quite unjustified by the original scientific evidence.
- Published
- 1995
23. Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia
- Author
-
Raymond G. Schlienger, Miriam Chipimo, Eric M. Njunju, Evans Mpabalwani, Melba Gomes, Frank M. Sullivan, Christine Manyando, Moses Sinkala, Mailis Virtanen, Verena Walter, Isabela Ribeiro, Lwipa Puma, Rhoda Mkandawire, and Marc Cousin
- Subjects
Adult ,Male ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Artemether/lumefantrine ,Adolescent ,lcsh:RC955-962 ,Zambia ,Abortion ,lcsh:Infectious and parasitic diseases ,Cohort Studies ,Antimalarials ,Young Adult ,Pregnancy ,Humans ,Medicine ,lcsh:RC109-216 ,Prospective Studies ,Artemether ,Pregnancy Complications, Infectious ,Prospective cohort study ,Perinatal Mortality ,Fluorenes ,business.industry ,Obstetrics ,Research ,Artemether, Lumefantrine Drug Combination ,Infant, Newborn ,medicine.disease ,Survival Analysis ,Artemisinins ,Malaria ,Drug Combinations ,Low birth weight ,Infectious Diseases ,Ethanolamines ,Gestation ,Female ,Parasitology ,medicine.symptom ,business ,Cohort study ,medicine.drug - Abstract
Background Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited. This prospective cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine (AL) in pregnant women with malaria. Methods Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode (AL vs. sulphadoxine-pyrimethamine, SP). Safety was assessed using standard and pregnancy-specific parameters. Post-delivery follow-up was six weeks for mothers and 12 months for live births. Primary outcome was perinatal mortality (stillbirth or neonatal death within seven days after birth). Results Data from 1,001 pregnant women (AL n = 495; SP n = 506) and 933 newborns (AL n = 466; SP n = 467) showed: perinatal mortality (AL 4.2%; SP 5.0%), comprised of early neonatal mortality (each group 2.3%), stillbirths (AL 1.9%; SP 2.7%); preterm deliveries (AL 14.1%; SP 17.4% of foetuses); and gestational age-adjusted low birth weight (AL 9.0%; SP 7.7%). Infant birth defect incidence was 1.8% AL and 1.6% SP, excluding umbilical hernia. Abortions prior to antenatal care could not be determined: abortion occurred in 4.5% of women treated with AL during their first trimester; none were reported in the 133 women exposed to SP and/or quinine during their first trimester. Overall development (including neurological assessment) was similar in both groups. Conclusions These data suggest that exposure to AL in pregnancy, including first trimester, is not associated with particular safety risks in terms of perinatal mortality, malformations, or developmental impairment. However, more data are required on AL use during the first trimester.
- Published
- 2010
24. Molybdenum Exposure and Semen Quality: How Robust Is the Evidence of an Effect?
- Author
-
Tom Sorahan and Frank M. Sullivan
- Subjects
Adult ,Male ,Infertility ,Adolescent ,Health, Toxicology and Mutagenesis ,Population ,Semen ,Andrology ,Semen quality ,Correspondence ,Linear regression ,Humans ,Medicine ,education ,Infertility, Male ,Sperm motility ,Molybdenum ,education.field_of_study ,business.industry ,Public Health, Environmental and Occupational Health ,Environmental exposure ,Middle Aged ,medicine.disease ,Sperm ,Lead ,Perspecitives ,business ,Cadmium ,Demography - Abstract
Meeker et al. (2008) reported on associations between blood levels of nine different metals and four aspects of semen quality found in 219 volunteers attending two infertility clinics. Based on the title of their article, it seems that the authors claimed to have found evidence that molybdenum is a male reproductive toxicant. But how robust is the evidence? Meeker et al. (2008) had no primary prior hypotheses, and their study was essentially a “fishing expedition” involving many statistical tests of many possible associations. The authors (Meeker et al. 2008) did note that “some [findings] may be chance findings because of the number of comparisons that were made.” A much stronger statement is appropriate, namely, that it is very likely that some of the findings were chance findings. The overwhelming majority of study subjects (70%) had blood Mo levels below the study limit of detection of 1 μg/L. If a more sensitive assay method had been used [e.g., the method of Case et al. (2001) with a detection limit of 0.06 μg/L], then a better grouping of subjects could have been used in the data analyses. We also believe the authors made an inappropriate analytical decision. In Table 3 of their article, Meeker et al. (2008) summarized analyses in which dose-dependent associations for each metal were considered in turn while adjusting for age and current smoking. The analysis of associations between Mo concentrations and semen motility were based on data from 147 subjects. The assumption appears to be that 72 (219 – 147) subjects had no useful information to provide on the Mo/sperm motility issue. It would have been more scientifically rigorous to allow the analysis of each semen parameter to make use of data from all study subjects, and not just for the sake of completeness. The current approach has introduced bias into the analysis, because different standards are applied to cases [subjects with the adverse health outcome of interest (e.g. poor sperm concentration)] and controls or referents (subjects without the adverse health outcome). To be concrete, in the analyses of sperm concentrations, cases were allowed to have poor sperm motility, whereas controls were not. The effect of this, in practice, is to load the controls with subjects on high incomes who have never smoked. A more standard analysis involving all study subjects in the analysis of each aspect of sperm quality should have been carried out. Such an analysis would likely have provided very different results to the subset analyses they reported. In commenting on the linear regression analyses shown in their Table 4, Meeker et al. (2008) stated that the Mo groups “were associated with suggestive decreasing trends in sperm concentration and morphology.” However, examination of the table shows that neither of the regression coefficients was significantly different from zero (i.e., the blood Mo level had no significant influence on any of the semen quality parameters). Additional studies would be needed to investigate possible effects in semen quality based on much larger population samples containing a wider range of blood Mo levels.
- Published
- 2009
25. Screening for left ventricular systolic dysfunction using GP-reported ECGs
- Author
-
Barclay M, Goudie, Rob I, Jarvis, Peter T, Donnan, Frank M, Sullivan, Stuart D, Pringle, Sanjay, Jeyaseelan, and Allan D, Struthers
- Subjects
Electrocardiography ,Ventricular Dysfunction, Left ,Cross-Sectional Studies ,Scotland ,Predictive Value of Tests ,Humans ,Clinical Competence ,Family Practice ,Referral and Consultation ,Sensitivity and Specificity ,Original Papers ,Health Services Accessibility - Abstract
Diagnostic echocardiography has poor access for patients with suspected heart failure. Pre-echocardiography screening with electrocardiograms (ECGs) is recommended as a means of targeting this scarce resource. There are data to support this policy when ECGs are interpreted by cardiologists but not by GPs.To assess the value of GP-reported ECGs as a pre-echocardiography screening test for left ventricular systolic dysfunction (LVSD).Cross-sectional study of GPs' ECG reporting skills.General practice, NHS in Scotland.A randomly selected, stratified sample of 123 Scottish GPs reviewed 180 ECGs (100 abnormal, 50 normal and 30 duplicate) from 150 patients with suspected heart failure. Forty-one patients had LVSD on echocardiography. GPs were required to categorise ECGs as normal or abnormal.Mean sensitivity was 0.94 (95% CI = 0.92 to 0.95). Mean specificity 0.58 (95% CI = 0.56 to 0.60). Mean positive predictive value (PPV) was 0.47 (95% CI = 0.46 to 0.48). Mean negative predictive value (NPV) was 0.96 (95% CI = 0.95 to 0.97). Mean likelihood ratio was 2.39 (95% CI = 2.28 to 2.50). Seventy of 123 (57%) GPs achieved sensitivity of 0.9 and specificity of 0.5 for the detection of LVSD.Most Scottish GPs have the skills to perform pre-echocardiography screening ECGs in patients with suspected LVSD. However, differences in ECG reporting performance between individual GPs will result in widely varying referral rates for echocardiography and differences in the detection rate of LVSD. The implications of these findings need to be considered when heart failure diagnostic services are being developed.
- Published
- 2007
26. Analysis of reproductive toxicity and classification of glufosinate-ammonium
- Author
-
Olavi Pelkonen, Franz Oesch, Diether Neubert, Rob Kroes, Lewis B. Holmes, Sir Colin Berry, Rolf Schulte-Hermann, Erminio Giavini, Heinz Nau, Frank M. Sullivan, Gerald N. Wogan, Tilmann Ott, Elisabeth Robert-Gnansia, Andrew Czeizel, and Nigel A. Brown
- Subjects
Pregnancy ,No-Observed-Adverse-Effect Level ,No-observed-adverse-effect level ,Offspring ,Herbicides ,Aminobutyrates ,Reproduction ,Physiology ,General Medicine ,Environmental Exposure ,Biology ,Toxicology ,medicine.disease ,Embryo, Mammalian ,Glutamine ,Animal data ,Glutamine synthetase ,medicine ,Conceptus ,Animals ,Humans ,Female ,Reproductive toxicity - Abstract
CONCLUSION REGARDING CLASSIFICATION OF GLUFOSINATE-AMMONIUM: Science Partners' Evaluation Group (Evaluation Group) has conducted an independent analysis of the herbicide glufosinate-ammonium (GA) relative to its potential to cause reproductive toxicity in humans. Further, the Evaluation Group has evaluated the implementation of Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC) and Council Directive 91/414/EEC, with respect to classification of chemicals posing potential reproductive hazards. After consideration of all information available to us relevant to the potential of glufosinate-ammonium (GA) to cause reproductive toxicity, the Science Partners Evaluation Group concludes that no classification of GA is justified. The following form the basis of this conclusion. There are no human data to suggest that GA causes reproductive toxicity in women or in their conceptus. The issue concerning possible reproductive hazard to humans is raised solely on the basis of positive animal test results that show GA to cause preimplantation or implantation losses in rats. SPECIFICALLY: a. Daily treatment with GA had no detectable effect on the earliest stages of the reproductive sequence including gametogenesis, ovulation, mating and conception; b. Treatment with GA interfered with rat gestation before and at the stage when the conceptus implants into the uterus. This effect occurred at doses of 360 ppm in the feed (corresponding to daily doses of 27.8 mg/kg bw) and above; and c. After implantation, no further effect of GA on prenatal and post-natal development was recognized. Previous concerns that GA might be toxic to embryonic stages after implantation were not supported by the data. Abortions and stillbirth seen were associated with, and regarded as secondary to, maternal toxicity. There was no evidence suggesting the induction of malformations in the offspring. The mechanism underlying this adverse effect in experimental laboratory animals is identified-inhibition of glutamine synthetase. Glutamine is essential to the viability of the embryo. The embryo is dependent on a maternal source of the amino acid. For embryo lethality to occur, a significant reduction of maternal glutamine is required. Such reduction in maternal glutamine depends on a significant inhibition of glutamine synthetase by GA. This can only occur when the mother is exposed to very high levels of GA. SPECIFICALLY: a. The reproductive toxicity of GA is confined to very short, early stages of reproduction, during which the conceptus is dependent on maternal glutamine; and b. In order for the effect to occur, significant reduction in maternal blood glutamine level is required, which in turn depends on a significant inhibition of glutamine synthetase, induced by high levels of GA in the maternal system. There is no evidence for accumulation of GA in the mammalian organism beyond a factor of two and no evidence for its metabolic toxification. To raise a concern in humans, women would have to be exposed to GA during the very limited time frame of preimplantation or implantation and the exposure would have to be to the exceedingly high levels necessary to alter the maternal metabolism and, correspondingly, result in glutamine levels in maternal tissue and blood plasma being drastically reduced. There is no basis to suggest that such exposures would occur under conditions of normal handling and use. SPECIFICALLY: a. Under conditions of normal handling and use, operators would never be exposed to GA levels that could potentially inhibit glutamine synthetase to the extent that this inhibition could impair preimplantation or implantation. b. All acceptable exposure measurements and predictive calculations confirm this conclusion, and in fact demonstrate that reasonably foreseeable exposure of workers would be to levels significantly below the AOEL. c. The evidence is also clear that there is no reproductive toxicity hazard to workers upon reentry tosprayed fields, bystanders, consumers or toddlers. The safety margin compared to the NOAEL in animal studies is sufficiently large to assure protection of the health of workers using GA as well as bystanders, consumers, and toddlers. Pursuant to Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC), to justify a classification of category 2 there must be sufficient evidence to produce a strong presumption that human exposure to the substance may result in impaired fertility in humans. It is the conclusion of the Science Partners Evaluation Group that there is no reasonable evidence to suggest a strong presumption of impairment. To the contrary, there is clear evidence demonstrating a strong presumption that exposure to GA would not cause the adverse effect demonstrated in rats. Pursuant to Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC), to justify a classification of category 3, there must be sufficient evidence to provide a strong suspicion of impaired fertility in humans. There is no basis to conclude that the animal data demonstrating impaired preimplantation or implantation has any relevance to humans in that the effect found in rats only occurs at levels which would never be experienced by workers under conditions of normal handling and use or by bystanders, consumers, or toddlers.
- Published
- 2005
27. Whole population secondary prevention of coronary heart disease in Scotland: the HEARTS database
- Author
-
Frank M, Sullivan, Peter T, Donnan, and Tom, Love
- Subjects
Databases, Factual ,Medical Records Systems, Computerized ,Scotland ,Vocabulary, Controlled ,Myocardial Infarction ,Humans ,Coronary Disease ,Medical Record Linkage ,Preventive Medicine ,Angioplasty, Balloon, Coronary ,Coronary Artery Bypass - Abstract
Implementing the evidence base for the management of chronic disease is as challenging as discovering which interventions are effective. The HEARTS collaboration (Heart disease Evidence-based Audit and Research in Tayside Scotland) is achieving that goal for the secondary prevention of coronary heart disease (CHD by linking national databases to manually validated hospital and family practice electronic patient records. Specific data from the system is fed back to practices in a facilitated educational process and through the NHS intranet. This paper describes some of the key features of this strategic decision support system. All residents of the Tayside region of Scotland (n=484,013 mid year estimate 2002) are covered by the system. 9,828 patients who have suffered a myocardial infarction(MI) or who have undergone angioplasty or bypass surgery are registered on the system. Improvements in clinical status and prescribing of effective therapies are 5-10% greater than elsewhere in Scotland.
- Published
- 2004
28. Summary: International Symposium on the Health Effects of Boron and its Compounds
- Author
-
Frank M. Sullivan and Ernest Mastromatteo
- Subjects
inorganic chemicals ,Male ,Health, Toxicology and Mutagenesis ,chemistry.chemical_element ,Toxicology ,chemistry.chemical_compound ,Human health ,Risk Factors ,Medicine ,Animals ,Humans ,Dietary Boron ,Boron ,Dose-Response Relationship, Drug ,Borax ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,Nutritional Requirements ,Environmental ethics ,Human physiology ,chemistry ,Female ,business ,Research Article - Abstract
Many of you have seen me worriedly writing in the corner, sometimes furiously, trying to get down all the very important points that the conference speakers were making. It is now my task to try to sum up this conference and to give you my idea of the implications for human health on the basis of the latest information presented here. There was a wide range of papers, including the chemical and physical prop? erties of the element and its compounds; their uses; the various methods for the analysis of boron in plants, animals, and humans, as well as in air, water and soil; the biochemical and pharmacological effects of boron in plants, animals, and humans; the effects of dietary boron in experimental ani? mals; the effects of boron in human nutri? tion and human physiology; the toxicology of boric acid and borax, including develop? mental and reproductive toxicity; and the assessment of health effects among workers exposed to boric acid and borates in their
- Published
- 1994
29. Significance of excursions of intake above the acceptable daily intake: effect of time and dose in developmental toxicology
- Author
-
Frank M. Sullivan
- Subjects
Acceptable daily intake ,Time Factors ,Birth weight ,Cmax ,Developmental toxicity ,Physiology ,Biology ,Toxicology ,Hazardous Substances ,Embryonic and Fetal Development ,Pregnancy ,medicine ,Animals ,Humans ,Dose-Response Relationship, Drug ,Area under the curve ,Abnormalities, Drug-Induced ,General Medicine ,medicine.disease ,Teratology ,Area Under Curve ,Prenatal Exposure Delayed Effects ,Toxicity ,Female ,Maximum Allowable Concentration - Abstract
Three major factors to be considered in assessing the possible effects on developmental toxicology of excursions above the acceptable daily intake (ADI) are discussed. If maternal toxicity occurs at lower doses than developmental toxicity, then there may be adequate protection for the fetus if the mother is protected. In other cases, the first adverse developmental effects are usually small and reversible changes in fetal weight and it is unlikely that brief excursions, for a few days, above the ADI, would induce changes in final birth weight. The importance of excursions above the ADI on teratogenic responses would likely depend on the mechanism of teratogenesis and whether the agent acted primarily as a result of a high peak plasma level, a Cmax effect, or depended more on the total body exposure, an area under the curve (AUC) effect. This type of information is usually not available from current safety study designs. Finally, the temporal equivalence factors must be taken into account. There are 10- to 100-fold differences in time span for pre- and postnatal development up to sexual maturity, in rodents compared with humans. This can be contrasted with the relatively small pharmacokinetic differences, perhaps of up to 2- or 3-fold in plasma levels of chemicals with the same administered dose in the two species. Thus, single episodes of high chemical exposure have greater opportunity to produce permanent effects on development in rodents compared with humans. The limited evidence from acute poisonings in pregnant women tends to support this hypothesis and it seems unlikely that occasional excursions by women above the ADI would result in developmental toxic effects.
- Published
- 1999
30. The European Community Directive on the classification and labeling of chemicals for reproductive toxicity
- Author
-
Frank M. Sullivan
- Subjects
Male ,European community ,business.industry ,Reproduction ,Public Health, Environmental and Occupational Health ,Directive ,Hazardous Substances ,Toxicology ,Teratogens ,Pregnancy ,Environmental health ,Occupational Exposure ,Medicine ,Humans ,European commission ,Female ,European Union ,Reproductive toxicity ,business ,Breast feeding ,Council directive - Abstract
The classification and labeling of dangerous substances was first introduced in 1967 in the European Community with Council Directive 67/548/EEC, known as the Dangerous Substances Directive. The Sixth Amendment to this directive in 1979 introduced a notification procedure for new chemicals and a requirement for labeling chemicals for toxicity. Three special categories for labeling were for carcinogenicity, mutagenicity, and teratogenicity. The teratogenicity classification was restricted to chemicals inducing teratogenic effects in the classical sense of the word, ie, producing only gross structural malformations. Discussions by expert advisors to the European Commission over several years led to a widening of concern in this area of toxicology and, under the recent Seventh Amendment,1 the classification of “teratology” has been changed to “toxic to reproduction.” This includes adverse effects on fertility, pre- and postnatal development, and lactation, and encompasses not only structural but also functional deficits. This will bring about a major change in the testing requirements to allow adequate classification of chemicals for these other aspects of reproductive toxicity.
- Published
- 1995
31. The European Community classification of chemicals for reproductive toxicity
- Author
-
Frank M. Sullivan
- Subjects
European community ,Reproduction ,General Medicine ,Biology ,Directive ,Toxicology ,Teratogens ,Pregnancy ,Environmental health ,Labelling ,Animals ,Humans ,Lactation ,European commission ,Female ,European Union ,Reproductive toxicity ,Council directive - Abstract
The classification and labelling of dangerous substances was first introduced in 1967 in the European Community with Council Directive 67/548/EEC known as the Dangerous Substances Directive. The “6th Amendment” to this directive in 1979 introduced a notification procedure and a requirement for labelling chemicals for toxicity. Three special categories for labelling were for “Carcinogenicity, Mutagenicity and Teratogenicity”. The teratogenicity classification was restricted to chemicals inducing “teratogenic” effects in the classical sense of the word ie. producing only gross structural malformations. Discussions by expert advisors to the European Commission over several years has lead to a widening of concern in this area of toxicology and under the forthcoming “7th Amendment” the classification of “Teratology” will be changed to “Toxic to Reproduction”. This will include adverse effects on fertility, pre- and postnatal development and lactation and will encompass not only structural but also functional deficits. This will bring about a major change in the testing requirements to allow adequate classification of chemicals for these other aspects of reproductive toxicity.
- Published
- 1992
32. Optimal strategies for identifying patients with myocardial infarction in general practice.
- Author
-
Peter T Donnan, Hamish T Dougall, and Frank M Sullivan
- Subjects
CORONARY disease ,FAMILY medicine ,MYOCARDIAL infarction - Abstract
Background. In order to provide evidence-based secondary prevention of coronary heart disease (CHD) in general practice, eligible patients need to be identified. The optimal strategy is one in which all appropriate patients are identified with the least effort. Objective. The purpose of the study was to determine the optimal strategy to identify subjects with a myocardial infarction (MI) from general practice records using different search criteria. Methods. The study was a cross-sectional survey of 10 general practices in Tayside, Scotland. A random sample of all subjects aged over 35 (n = 5061) and registered with the general practices was obtained. The main outcome measures were sensitivity, specificity, positive predictive value (PPV) and yield (the number of records that need to be examined to detect a 'true case'). Results. Of the sample of 5061, 207 (4.1%) were defined to have had a 'gold standard' MI. A Read code for ischaemic heart disease (IHD) had the highest sensitivity (95%) but with a poor PPV (52%). All searches had high specificities. The addition of a record of hospitalization for MI to the Read code for MI gave 100% sensitivity and high yield (1 in 1.11). In situations where the Read coding is of poor quality, the alternative search strategy of a hospital record of MI or receiving aspirin or nitrates was optimum. Conclusions. Patients who had experienced an MI can be easily identified from a combination of a Read code for MI and a record of hospitalization for an MI giving 100% sensitivity and specificity with a yield of 1 in 1.11. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
33. Impact of the Environment on Reproduction from Conception to Parturition
- Author
-
Frank M. Sullivan
- Subjects
Vitamin ,Alcohol Drinking ,Health, Toxicology and Mutagenesis ,Biology ,Hazardous Substances ,Toxicology ,chemistry.chemical_compound ,Human reproduction ,Embryonic and Fetal Development ,Pregnancy ,Environmental health ,medicine ,Humans ,Nutritional Physiological Phenomena ,business.industry ,Smoking ,Public Health, Environmental and Occupational Health ,Environmental exposure ,Environmental Exposure ,medicine.disease ,Embryo, Mammalian ,chemistry ,Socioeconomic Factors ,Food processing ,Food Microbiology ,Female ,Reproductive toxicity ,business ,Polychlorinated dibenzofurans ,Research Article - Abstract
Consideration of environmental influences on human reproduction must include an investigation of the socioeconomic factors that play an important role in embryo-fetal development. Nutritional factors are of prime importance, and modern methods of food production and supply have led to new hazards for pregnant women. For example, pregnant women have been advised in a number of European countries not to eat liver due to the very high concentration (frequently exceeding 100,000 IU per 100 g) of vitamin A. The clear demonstration that periconceptional vitamin supplementation can dramatically reduce the recurrence rate of neural tube defects suggests that folic acid deficiency may be common even in otherwise well-nourished women. Modern methods of food production manufacture and sale have increased the risks of Salmonella and Listeria infections in pregnancy. The dangers of social drug use, especially alcohol and tobacco, are discussed. The types of adverse effect that can result from chemical exposure during the different stages of pregnancy is reviewed with a discussion of some of the problems of epidemiological studies in attempting to identify toxic chemicals. The extent of the ignorance concerning the reproductive toxicity of industrial and environmental chemicals is emphasized by the fact that data are available on only a small percentage of even the high-production volume (1000 tons/year) chemicals. The evidence of reproductive toxicity from exposure to lead, methyl mercury, polychlorinated biphenyls, polychlorinated dibenzofurans, and hexachlorobenzene are briefly reviewed. Some areas of research needs are discussed with emphasis on nutrition, food production, preparation, and storage and the new problems that may be introduced by genetic manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
34. Problems in the long-term assessment of risks from drugs used in pregnancy maintenance*
- Author
-
Frank M. Sullivan
- Subjects
Risk ,medicine.medical_specialty ,Drug Administration Schedule ,Pregnancy ,Epidemiology ,medicine ,Humans ,Longitudinal Studies ,reproductive and urinary physiology ,Fetus ,business.industry ,Obstetrics ,Rehabilitation ,Obstetrics and Gynecology ,Estrogens ,medicine.disease ,Term (time) ,Threatened abortion ,Pregnancy Complications ,Reproductive Medicine ,Pregnancy Maintenance ,Female ,Progestins ,Epidemiologic Methods ,business ,Hormone - Abstract
Progestogens and oestrogens used to maintain pregnancy in cases of threatened abortion could have side-effects on the mother or fetus. The difficulties in interpreting epidemiological studies on the effects of sex hormones on pregnancy are discussed in relation to the combination of hormones employed, their purpose, time of usage and dosage.
- Published
- 1986
35. Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings
- Author
-
Elizabeth Elefant, Ushma Mehta, Mackensie Yore, Max Petzold, Esperança Sevene, Melba Gomes, Frank M. Sullivan, Viviana Mangiaterra, Elizabeth Allen, Jan Singlovic, Lewis B. Holmes, Christine Clerk, Division of Clinical Pharmacology, and Faculty of Health Sciences
- Subjects
medicine.medical_specialty ,Pediatrics ,Databases, Factual ,Drug exposure ,Reproductive medicine ,Developing country ,Disease ,Prenatal care ,World Health Organization ,lcsh:Gynecology and obstetrics ,Study Protocol ,Pharmacovigilance ,Antimalarials ,Teratogenicity ,Pregnancy ,Obstetrics and Gynaecology ,Medicine ,Humans ,Maternal Health Services ,Congenital anomaly ,Registries ,lcsh:RG1-991 ,business.industry ,Pregnancy Registry ,Public health ,Medical record ,Pregnancy Outcome ,Obstetrics and Gynecology ,Abnormalities, Drug-Induced ,Antiretrovirals ,Neonates ,Prenatal Care ,medicine.disease ,Resource-limited settings ,Birth defects ,Family medicine ,Female ,Safety ,business - Abstract
Background The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy. Methods/Design Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed. Discussion In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improve maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.
- Full Text
- View/download PDF
36. Animal Tests to Screen for Human Teratogens
- Author
-
Frank M. Sullivan
- Subjects
embryonic structures ,Pediatrics, Perinatology and Child Health - Abstract
Despite Dr. Brent's statement earlier that animal models are not good for teratologic testing, they are all that we have at the moment. It is not reasonable to use new compounds without some preliminary experimental teratology, and it is not reasonable to think we can use human beings for toxicological screening of new compounds. Therefore, I should like to describe briefly, especially for the clinicians present, several aspects of teratologic testing in animals. First the question, "Is a given drug teratogenic?" To my mind that is the same type of question as, "Is a given drug toxic?" because teratogenesis is just one aspect of toxicology. For almost any compound someone could devise a system to show that it is teratogenic. When a drug or chemical is administered to a pregnant animal, it can affect either the mother first or the fetus first. If the fetus is more sensitive, low doses may produce malformations. At higher doses more severe effects occur, namely lethality. At still higher doses, the mothers themselves become ill. If the mother is more sensitive, no effects are observed on the fetus until the mother receives near-lethal doses, at which time one begins to see abnormal or defective fetuses. We have found that, generally, drugs which are teratogenic for the fetus at almost toxic levels for the mother are rather safe. Drugs that are teratogenic at doses much lower than the toxic levels for the mother are, on the whole, unsafe. The judgment is made without regard to the therapeutic dose of the drug.
- Published
- 1974
37. Book Reviews
- Author
-
FRANK M SULLIVAN
- Subjects
Epidemiology ,General Medicine - Published
- 1984
38. Health outcomes following liver function testing in primary care: a retrospective cohort study.
- Author
-
David J McLernon, Peter T Donnan, Stephen Ryder, Paul Roderick, Frank M Sullivan, William Rosenberg, and John F Dillon
- Subjects
LIVER function tests ,HEALTH outcome assessment ,PRIMARY care ,COHORT analysis ,LIVER diseases ,POPULATION health ,PATIENTS - Abstract
Background. patients who present with abnormal liver function tests (LFTs) in primary care and no obvious symptoms can be difficult to manage. Objective. The objective is to follow-up a cohort of liver function tested patients to determine their outcome. Methods. This population-based retrospective cohort study was conducted in Tayside, Scotland, from 1989 to 2003. Subjects were patients with no clinically obvious liver disease at initial liver function testing in primary care. Main outcomes were diagnosed liver disease and mortality. Record linkage of databases ascertained risk factors and outcomes. Measures of performance were calculated and Weibull regression analysis from initial LFT date was performed on all outcomes by level of abnormality. Results. In total, 95 977 patients had 364 194 incident initial LFTs, with median follow-up 3.7 years. A total of 21.7% had at least one abnormal LFT and 1108 (1.15%) developed liver disease. Elevated transaminase was strongly associated with diagnosed liver disease, hazard ratio (HR) = 4.23 (95% confidence interval 3.55, 5.04) for mild levels and HR = 12.67 (95% CI 9.74, 16.47) for severe levels versus normal. For gamma-glutamyl transferase, these hazards were 2.54 (95% CI 2.17, 2.96) and 13.44 (95% CI 10.71, 16.87), respectively. Low albumin was strongly associated with all-cause mortality, HR = 2.65 (95% CI 2.47, 2.85) for mild levels and HR = 4.99 (95% CI 4.26, 5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity high. Conclusions. All LFTs were predictive markers for liver disease as well as general ill health, although sensitivity was poor. Most patients with abnormal LFTs had no later formal diagnosis of liver disease within the study period. The time taken to develop liver disease in these patients provides opportunity to intervene. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.