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Biomedical subjects

J Head

Publications and source records attributed to J Head.

At least 37 records · Page 2Linked to original sources
PubMed1998

Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry.

OBJECTIVE: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson's disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions. DESIGN: Open randomised trial and blind comparison and reclassification of the cause of death of patients who were recruited from 93 hospitals between 1985 and 1990 and who had died before December 1993 in arms 1 and 2. SETTING: United Kingdom. SUBJECTS: 624 patients with early Parkinson's disease who were not receiving dopaminergic treatment and a subgroup fo 120 patients who died during the trial. INTERVENTIONS: Levodopa and a dopa carboxylase inhibitor (arm 1), levodopa and a dopa decarboxylase inhibitor in combination with selegiline (arm 2), or bromocriptine alone (arm 3). MAIN OUTCOME MEASURES: All cause mortality for 520 subjects in arms 1 and 2 and for 104 subjects who were randomised into these arms from arm 3. Cause specific mortality for people who died in the original arms 1 and 2 on the basis of the opinion of a panel, revised diagnosis and disability ratings, evidence from clinical records of either autonomic or cardiovascular episodes, other clinical features before death, and drug interactions. RESULTS: After extended follow up (mean 6.8 years) until the end of September 1995, when arm 2 was terminated, the hazard ratio for arm 2 compared with arm 1 was 1.32 (95% confidence interval 0.98 to 1.79). For subjects who were randomised from arm 3 the hazard ratio for arm 2 was 1.54 (0.83 to 2.87). When all subjects were included the hazard ratio was 1.33 (1.02 to 1.74) and after adjustment for other baseline factors it was 1.30 (0.99 to 1.72). The excess mortality seemed to be greatest in the third and fourth year of follow up. Cause specific death rates showed an excess of deaths from Parkinson's disease only (hazard ratio 2.5 (1.3 to 4.7)). No significant differences were found for revised diagnosis, disability rating scores, autonomic or cardiovascular events, other clinical features, or drug interactions. Patients who died in arm 2 were more likely to have had possible dementia and a history of falls before death compared with those who died in arm 1. CONCLUSION: The results consistently show excess mortality in patients treated with combined levodopa and selegiline. Revised diagnosis, autonomic or cardiovascular events, or drug interactions could not explain this finding, but falls and possible dementia were more common in arm 2. The results do not support combined treatment in patients with newly diagnosed Parkinson's disease. In more advanced disease, combined treatment should perhaps be avoided in patients with postural hypotension, frequent falls, confusion, or dementia.

Antiparkinson Agents↗
PubMed1998

Explaining social class differences in depression and well-being.

Work characteristics, including skill discretion and decision authority, explain most of the socioeconomic status gradient in well-being and depression in middle-aged British civil servants from the Whitehall II Study, London. Social support explained about one-third of the gradient, life events and material difficulties less than one-third. Socioeconomic status was measured by employment grade. Work characteristics were based on the Karasek model, social support was measured by the Close Persons Questionnaire, depression by the General Health Questionnaire and well-being by the Affect Balance Scale. Despite a small contribution from social selective factors measured by upward mobility, the psychosocial work environment explained most of the cross-sectional socioeconomic status gradient in well-being and depression.

Adult↗
PubMed1998

Socioeconomic and sex differentials in reason for sickness absence from the Whitehall II Study.

OBJECTIVES: Large socioeconomic differences exist in disease and mortality. This paper describes the distribution of specific medical reasons for sickness absence by grade of employment in the Whitehall II study and validates the medical reason by comparison with general practitioners' records. METHODS: Analysis of sickness absence data on 5620 male and female civil servants aged 35-55 years. Data have been collected from 12 of the 20 London based civil service departments participating in the Whitehall II study, where medical reason for absence was available. Rates and distributions of reasons for absence for short spells (< or = 7 days) and long spells (> 7 days) were analysed. RESULTS: Respiratory disorders and gastroenteritis accounted for over half of all spells of absence, with headache and migraine, musculoskeletal disorders, injury, and neurosis accounting for a further 20%-30% of absences. There was an inverse association with employment grade, the lower the grade the higher the rate of absence for both short spells (< or = 7 days) and long spells (> 7 days). In general, women had higher rates of absence than men. Comparison of reason for very long spells of absence (> 21 days) showed moderate agreement between civil service and general practitioner. CONCLUSION: There is a lack of national comprehensive data on sickness absence and medical reason for absence, in particular for women and for spells of different duration. Data from the Whitehall II study show large employment grade and sex differences in the distribution of medical reasons for absence that are similar to socioeconomic differences in morbidity documented in other studies. Possible explanations include the subjective nature of illness and disease; the work/family interface; and the influence of the absence culture. Longer term follow up will provide information on whether sickness absence relates to serious morbidity and mortality.

Absenteeism↗
PubMed1997

Work and psychiatric disorder in the Whitehall II Study.

It is important that the effects of work on mental health are investigated when work practices are changing rapidly and there is decreasing job security. This has been examined in the Whitehall II Study, a cohort study of 6895 male and 3413 female, London-based civil servants, aged 35-55 years at baseline in 1985. Work characteristics were measured by modified Karasek indices in a self-report questionnaire. Psychiatric disorder was measured by the 30-item General Health Questionnaire (GHQ). In longitudinal analyses in men and women, high work social support predicted lower GHQ scores, and high job demands predicted higher GHQ scores at follow-up. High work social support and high skill discretion were protective against taking short spells of psychiatric sickness absence. The protective effects of social support at work and the potential risk of job demands have implications for management, job design, training, and further research.

Adult↗
PubMed1997

Social support and psychiatric sickness absence: a prospective study of British civil servants.

BACKGROUND: Studies on the direct and buffering effects of social support have not examined psychiatric sickness absence and few studies have considered support both at home and at work. This study addresses prospectively the effects of chronic stressors and social supports, at home and at work, on psychiatric sickness absence rates. METHODS: Sociodemographic factors, health and social support were measured at baseline, and short and long spells of sickness absence were measured prospectively over a 5-year period. The participants were a subsample of 4202 male and female civil servants, aged 35-55 years at baseline, from an occupational cohort, the Whitehall II Study, who completed detailed social support questions. RESULTS: Support from colleagues and supervisors at work is related to lower risk of short spells of psychiatric sickness absence, particularly for those also receiving high levels of negative aspects of close relationships from their closest person outside work. Negative aspects of close relationships from the closest person increase the risk of taking long spells of psychiatric sickness absence in men. High levels of material problems increase the risk of short spells of sickness absence. CONCLUSIONS: Negative aspects of close relationships may have an aetiological role in non-psychotic psychiatric disorder. Social support at work appears to protect against short spells of psychiatric sickness absence. This potentially implies that levels of short spells of absence might be reduced by increasing support at work. Conversely, emotional support at home may influenced absence-related behaviour and encourage a person to take absence at a time of illness.

Absenteeism↗
PubMed1996

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Excess mortality and its relation to hypertension and proteinuria in diabetic patients. The world health organization multinational study of vascular disease in diabetes.

OBJECTIVE: To determine the extent that mortality in IDDM and NIDDM patients is in excess of that of the general population and examine its relation to hypertension and proteinuria in diabetic patients. RESEARCH DESIGN AND METHODS: A stratified random sample of 4,714 diabetic patients aged 35-55 years participating in the World Health Organization Multinational Study of Vascular Disease in Diabetes has been followed up from 1975 to 1987. Excess mortality, compared with the background population, was assessed in terms of standardized mortality ratios (SMRs) for each of the 10 international cohorts. The relationship between excess mortality and proteinuria/hypertension was examined by diabetes type and sex. RESULTS: SMRs were in general higher in patients with IDDM (ranging from 188 to 686 for men and from 336 to 790 for women) than with NIDDM (from 138 to 370 for men and from 126 to 435 for women). For both diabetes types and in both sexes, SMRs decreased with increasing age and increased with increasing diabetes duration. Patients with both hypertension and proteinuria experienced a strikingly high mortality risk: 11-fold for men with IDDM and 18-fold for women with IDDM and 5-fold for men with NIDDM and 8-fold for women with NIDDM. Even in the absence of proteinuria and hypertension, SMRs were significantly increased in both IDDM (284 men and 360 women) and NIDDM (192 men and 236 women) patients. CONCLUSIONS: Considerable international differences were found not only in mortality rates for the two types of diabetes but also in the extent of excess mortality among centers. IDDM patients had a high excess mortality in comparison with the general population. The significant excess mortality was demonstrated even in patients without proteinuria and without hypertension for both sexes and diabetes types.

Adult↗
PubMed1995

Sickness absence for psychiatric illness: the Whitehall II Study.

Over the past 20 years, rates of sickness absence have increased and psychiatric disorders have become an important cause of sickness absence. The socio-demographic associations for psychiatric sickness absence are reported from the Whitehall II study, a longitudinal survey of 10,308 London-based male and female civil servants between 35-55 years. Short spells (< or = 7 days), long spells (> 7 days) and very long spells (> 21 days) of sickness absence were examined in 5620 civil servants for whom reason for absence was available in civil service records. Civil service coding of reasons for absence was validated against report of general practitioners' diagnoses. Psychiatric disorder, largely neurosis and neurosis ill-defined, was the third most common cause of long spells of sickness absence in women and the fourth most common in men. For both men and women it was the second most common cause of very long spells of absence. Psychiatric sickness absence for short, long and very long spells was more frequent in lower employment grades than higher employment grades in keeping with the pattern for other illnesses. This partly explains the higher rate of sickness absence in women than men. Widowed and single men, and divorced women had high rates of psychiatric sickness absence. Comparing reason codes based on sickness certificates with general practitioners reports, there appeared to be evidence of under-reporting of psychosis on certificates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Cancer mortality in Indian and British ethnic immigrants from the Indian subcontinent to England and Wales.

Risk of cancer mortality from 1973 to 1985 in persons born in the Indian subcontinent who migrated to England and Wales was analysed by ethnicity, and compared with cancer mortality in the England and Wales native population, using data from England and Wales death certificates. There were substantial highly significant raised risks in Indian ethnic migrants for cancers of the mouth and pharynx, gall bladder, and liver in each sex, larynx and thyroid in males, and oesophagus in females. There were also substantial raised risks in these migrants of each sex for non-Hodgkin's lymphoma and myeloma. For the mouth and pharynx, and liver in each sex, and gall bladder in females, there were also raised risks of lesser magnitude in British ethnic migrants. For colon and rectal cancer and cutaneous melanoma in each sex, ovarian cancer in women and bladder cancer in men, there were appreciable significantly reduced risks in the Indian ethnic migrants not shared by those of British ethnicity. Appreciable raised risks in British ethnic migrants not shared by those of Indian ethnicity occurred for nasopharyngeal cancer in males, soft tissue malignancy in both sexes and non-melanoma skin cancer in males. In migrants of both ethnicities there were appreciable significantly raised risks in each sex for leukaemia and decreased risks in each sex for gastric cancer, for lung cancer except in females of British ethnicity and in males for testicular cancer. The results suggest the need for public health measures to combat the high risks of oral and pharyngeal cancers and liver cancer in the Indian ethnic immigrant population of England and Wales, by prevention of betel quid chewing and hepatitis transmission respectively. The data also imply that early exposures or early acquired behaviours in India, or exposures during migration, may increase the risk of leukaemia and reduce the risks of gastric and testicular cancers in the migrants irrespective of their ethnicity. Aetiological studies would be worthwhile to investigate the reasons for the sizeable decreased risk of colon and rectal cancer and increased risk of gall bladder cancer in each sex and the increased risk of thyroid and laryngeal cancer in males and oesophageal cancer in females of Indian ethnicity but not of British ethnicity who have migrated from the Indian subcontinent.

Adolescent↗
PubMed1995

Sickness absence in the Whitehall II study, London: the role of social support and material problems.

STUDY OBJECTIVE: To investigate the role of social supports, social networks, and chronic stressors: (i) as predictors of sickness absence; and (ii) as potential explanations for the socioeconomic gradient in sickness absence. DESIGN: A prospective cohort study (Whitehall II study) with sociodemographic factors, health and social support measured at baseline, and spells of sickness absence measured prospectively. SETTING: Twenty London based non-industrial departments of the British civil service. PARTICIPANTS: Participants were civil servants (n = 10,308), aged 35-55 years at baseline, of whom 67% (6895) were men and 33% (3413) were women. The overall response rate for Whitehall II was 73% (74% for men and 71% for women). The analysis is based on 41% of the sample who had data on reasons for sickness absence and were administered all social support questions. Only 4.3% of participants did not complete all necessary questions and were excluded. MEASUREMENTS AND MAIN RESULTS: High levels of confiding/emotional support from the "closest person" predicted higher levels of both short and long spells of sickness absence. After adjusting for baseline physical and psychological health the effects were increased, suggesting that high levels of confiding/emotional support may encourage illness behaviour rather than generate illness. Social network measures showed a consistent but less striking pattern. Increased levels of negative aspects of social support resulted in higher rates of sickness absence. Material problems strongly predicted sickness absence, but the effect was diminished once adjustment for the covariables was made, suggesting that health status may be functioning as an intervening variable between chronic stressors and sickness absence. In addition, social support may buffer the effects of chronic stressors. Social support did not contribute to explaining the gradient in sickness absence by employment grade beyond that explained by the baseline covariables. CONCLUSIONS: Sickness absence from work is a complex phenomenon, combining illness and coping behaviours. High levels of confiding/emotional support, although not entirely consistent across samples, may either encourage people to stay at home when they are ill or may be accompanied by more social obligations at home prolonging sickness absence. Negative aspects of close relationships may jeopardize health and hence increase sickness absence.

Administrative Personnel↗
PubMed1993

Explaining socioeconomic differences in sickness absence: the Whitehall II Study.

OBJECTIVE: To describe and explain the socioeconomic gradient in sickness absence. DESIGN: Analysis of questionnaire and sickness absence data collected from the first phase of the Whitehall II study. Grade of employment was used as a measure of socioeconomic status. SETTING: 20 civil service departments in London. SUBJECTS: 6900 male and 3414 female civil servants aged 35-55 years. MAIN OUTCOME MEASURES: Rates of short spells (< or = 7 days) and long spells (> 7 days) of sickness absence. RESULTS: A strong inverse relation between grade of employment and sickness absence was evident. Men in the lowest grade had rates of short and long spells of absence 6.1 (95% confidence interval 5.3 to 6.9) and 6.1 (4.8 to 7.9) times higher than those in the highest grade. For women the corresponding rate ratios were 3.0 (2.3 to 3.9) and 4.2 (2.5 to 6.8) respectively. Several risk factors were identified, including health related behaviours (smoking and frequent alcohol consumption), work characteristics (low levels of control, variety and use of skills, work pace, and support at work), low levels of job satisfaction, and adverse social circumstances outside work (financial difficulties and negative support). These risk factors accounted for about one third of the grade differences in sickness absence. CONCLUSION: Large grade differences in sickness absence parallel socioeconomic differences in morbidity and mortality found in other studies. Identified risk factors accounted for a small proportion of the grade differences in sickness absence. More accurate measurement of the risk factors may explain some of the remaining differences in sickness absence but other factors, as yet unrecognised, are likely to be important.

Absenteeism↗
PubMed1993

Effect of needle changing and intravenous cannula collection on blood culture contamination rates.

STUDY OBJECTIVES: We tested the hypotheses that blood culture positivity and contamination rates were not increased by not changing needles between venipuncture and inoculation of blood culture bottles or by taking blood for culture by freshly inserted IV cannulae. DESIGN: A prospective study of blood cultures collected by venipuncture or IV cannulae taken from an emergency department population. Venipuncture samples were randomized into needle change (standard method) or no needle change before inoculation into blood culture bottles. PARTICIPANTS: Nine hundred forty patients requiring blood cultures after assessment in the ED. INTERVENTIONS: A standard disinfection procedure using 0.5% chlorhexidine in 70% alcohol was used. Blood was collected by venipuncture and inoculated with or without needle change. Blood collected by IV cannula was inoculated with a fresh needle applied to the collection syringe. MEASUREMENTS AND MAIN RESULTS: There was no statistically significant difference in contamination rates for blood collected by venipuncture with no needle change (6.4%) compared with needle change (4.2%, P > .30). No significant difference in contamination rates was noted for blood taken by freshly inserted IV cannulae (4.3%) compared with venipuncture with needle change after sampling (4.2%, P > .90). Some problems with randomization resulted in unequal numbers in the needle-change (286) versus no-needle-change (141) subgroups, and this may have introduced bias. A higher rate of pathogen growth was observed in blood taken by IV cannula (11.4%) compared with the standard method (6.3%) (P < .025). A significantly greater rate of Gram-negative sepsis was noted in the IV cannula group (6.6%) compared with direct venipuncture with needle change (1.1%) and no needle change (4.2%, P < .01). CONCLUSION: The results of this study do not support the practice of changing needles before inoculating blood samples into blood culture bottles. Collection of blood for culture through freshly inserted IV cannulae is associated with a low contamination rate and is an acceptable alternative to direct venipuncture. Sources of bias in this study suggest that further research is needed to determine the optimal technique for collecting blood cultures.

Bacteriological Techniques↗
PubMed1993

Alcohol consumption and sickness absence: from the Whitehall II study.

Previous studies suggest that problem drinkers have markedly increased sickness absence. However, it is not clear how more moderate alcohol consumption and abstinence relate to sickness absence. As part of the Whitehall II study the relationship between different drinking patterns and sickness absence is examined. A total of 10,314 male and female civil servants completed a baseline questionnaire about their drinking habits--the amount of alcohol consumed over the past 7 days and the frequency of drinking over the past 12 months. All sickness absence has been recorded prospectively. Drinking patterns and sickness absence are examined for short spells (< or = 7 days) and long spells (> 7 days) adjusting for other causes of sickness absence: age, grade of employment, smoking, work characteristics and baseline health. Alcohol consumption was strongly related to employment grade, the lower the grade the higher proportion of men and women reporting no alcohol consumption. For men the relation of alcohol intake to short spells of sickness absence (< or = 7 days) appeared to be U-shaped, for long spells (> 7 days) increased rates of absence were found only in frequent drinkers. There was no clear relationship for women, however higher rates of sickness absence were found in non-drinkers.

Absenteeism↗
PubMed1992

Cancer mortality in African and Caribbean migrants to England and Wales.

Cancer mortality during 1970-85 of immigrants from East and West Africa and the Caribbean to England and Wales is described. Overall cancer mortality was raised in West African males (RR 1.38, 95% CI 1.25-1.54), and non-significantly raised in West African females (RR 1.14, 0.96-1.37) compared to mortality in the England and Wales-born population. Much of the increased risk was due to very high rates of liver cancer in males (RR 31.6, 23.8-41.9), but rates were also raised for a wide range of other cancers in each sex. Only lung and brain cancer had significantly decreased mortality. In East Africans, overall cancer mortality was low in males (RR 0.63, 0.56-0.70), and in females (RR 0.80, 0.72-0.89). Mortality was significantly low for cancers of the stomach, pancreas and testis, and Hodgkin's disease in males, for cervical cancer in females, and for lung cancer and melanoma in both sexes. Cancer sites with significantly raised mortality included oropharyngeal cancer, leukaemia, and multiple myeloma in both sexes. In Caribbean immigrants overall cancer rates were significantly low in males (RR 0.71, 0.68-0.74) and in females (RR 0.76, 0.73-0.80). Mortality was significantly low for many cancers including colorectal, lung, testis and brain cancers. Mortality was significantly raised only for cancer of the prostate in males, of the placenta in females, and of the liver, non-Hodgkin's lymphoma and multiple myeloma in both sexes. Overall, mortality was high from prostatic cancer and liver cancer, and was low from brain cancer, in predominantly ethnic African immigrant groups. Both East and West African immigrants had raised rates of leukaemia. All of the migrant groups had high rates of multiple myeloma and low rates of testicular, ovarian and lung cancer. Genetic and environmental factors that may contribute to these patterns are discussed.

Adolescent↗