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A N Phillips

Publications and source records attributed to A N Phillips.

At least 181 records · Page 10Linked to original sources
PubMed1992

Smoking as "independent" risk factor for suicide: illustration of an artifact from observational epidemiology?

Two widely used criteria for determining whether an association between a risk factor and a disease is causal are dose response and independence from other factors. Data from a large US risk factor study (MRFIT) throw up a relation between cigarette smoking and suicide that meets these criteria, yet appears to be biologically implausible. It is likely that many more such associations, for other exposures and other diseases, are equally spurious, but are protected by their lack of obvious implausibility.

Adult↗
PubMed1992

Leukocyte count and risk of major coronary heart disease events.

The association between leukocyte count and subsequent risk of major coronary heart disease events was examined using data from three prospective cohort studies--two from the United States and one from Great Britain. A total of 28,181 middle-aged men were followed for 6-12 years. A total of 1,768 men had a nonfatal myocardial infarction or died of coronary heart disease. In all three cohorts, there was a positive, statistically significant relation between baseline leukocyte count and risk of subsequent major coronary heart disease events after adjustment for age, serum total cholesterol, diastolic blood pressure, and number of cigarettes smoked per day (relative odds = 1.32 (p less than 0.0001), 1.15 (p = 0.0001), and 1.14 (p = 0.003), corresponding to a 2,000/mm3 difference in leukocyte count). The associations persisted when all nonsmokers (former smokers plus never smokers) and never smokers alone were considered and when those with evidence of preexisting coronary heart disease at baseline were excluded. Leukocyte count appears to be an indicator of a person's future risk of major coronary heart disease events.

Adult↗
PubMed1992

The leukocyte count and risk of lung cancer.

The association between leukocyte count and subsequent risk of lung cancer was evaluated in three large cohorts from the United States and Britain. A total of 309 lung cancer events occurred among 28,181 men whose cases were followed-up for 7 to 12 years. In all three cohorts, there was a marked increase in risk of lung cancer with increasing leukocyte count, after adjustment for age and the number of cigarettes smoked per day. The adjusted relative odds in the three cohorts, for a 2000/microliters difference in leukocyte count, were 1.58 (P = 0.0001), 1.29 (P = 0.003) and 1.20 (P = 0.02). These relative odds persisted when current smokers were considered alone, when serum markers of cigarette smoking exposure were adjusted for, and when men with lung cancer events during the first 5 years of follow-up were excluded. The leukocyte count appears to be linked to the pathogenesis of smoking-related lung cancer.

Adult↗
PubMed1992

Bias in relative odds estimation owing to imprecise measurement of correlated exposures.

A series of graphs is presented that show the estimated degree of bias in logistic coefficient estimates for two correlated continuous exposures measured with imprecision. These graphs indicate that even when the correlation coefficient between the exposure of interest and a correlated exposure is as low as 0.2, imprecision in the measurement of the latter exposure can result in at least as serious bias in the logistic coefficient estimate for the exposure of interest as measurement imprecision in the exposure of interest itself. The implications for the design and interpretation of epidemiological studies are discussed.

Bias↗
PubMed1992

Cytomegalovirus (CMV) infection, CD4+ lymphocyte counts and the development of AIDS in HIV-1-infected haemophiliac patients.

After a maximum of 11 years (median 8.3 years) from the time of HIV seroconversion, 25 out of 59 (42%) of CMV-seropositive haemophiliacs had progressed to AIDS, as opposed to eight out of 50 (16%) CMV seronegatives. The age-adjusted relative risk for AIDS among CMV seropositives was 2.4 (P = 0.03). In order to determine how this adverse effect is mediated, the mean rate of decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts tended to decline more rapidly in CMV seropositives than in seronegatives (-0.087 x 10(9)/l per annum versus -0.082 x 10(9)/l per annum), but this difference did not reach statistical significance. The average CD4+ lymphocyte count at the time of HIV seroconversion was estimated to be similar in CMV seropositives and negatives, because in HIV-1-negative haemophiliacs the CD4+ counts were virtually identical, after adjustment for age (0.94 x 10(9)/l and 0.97 x 10(9)/l, respectively). The median CD4+ cell count at which AIDS developed was higher in the CMV-seropositive group (0.07 x 10(9)/l) than in the seronegative group (0.04 x 10(9)/l), but this difference did not reach statistical significance. We conclude from these findings that the adverse effect of CMV is not wholly mediated via a more rapid loss of CD4+ cells. We discuss other processes that may be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or dissemination of HIV in other organs, which may be important in determining the earlier onset of AIDS among CMV-seropositive subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis.

With the advent of standard flow cytometric methods using two-colour fluorescence on samples of whole blood, it is possible to establish the ranges of CD3, CD4 and CD8 T lymphocyte subsets in the routine laboratory, and also to assist the definition of HIV-1-related deviations from these normal values. In 676 HIV-1-seronegative individuals the lymphocyte subset percentages and absolute counts were determined. The samples taken mostly in the morning. The groups included heterosexual controls, people with various clotting disorders but without lymphocyte abnormalities as well as seronegative homosexual men as the appropriate controls for the HIV-1-infected groups. The stability of CD4% and CD8% values was demonstrated throughout life, and in children CD4 values less than 25% could be regarded as abnormal. The absolute counts of all T cell subsets decreased from birth until the age of 10 years. In adolescents and adults the absolute numbers (mean +/- s.d.) of lymphocytes, CD3, CD4 and CD8 cells were 1.90 +/- 0.55, 1.45 +/- 0.46, 0.83 +/- 0.29 and 0.56 +/- 0.23 x 10(9)/l, respectively. In patients with haemophilia A and B the mean values did not differ significantly. In homosexual men higher CD8 levels were seen compared with heterosexual men and 27% had an inverted CD4/CD8 ratio but mostly without CD4 lymphopenia (CD4 less than 0.4 x 10(9)/l). However, some healthy uninfected people were 'physiologically' lymphopenic without having inverted CD4/CD8 ratios. When the variations 'within persons' were studied longitudinally over a 5-year period, the absolute CD4 counts tended to be fixed at different levels. As a marked contrast, over 60% of asymptomatic HIV-1+ patients exhibited low CD4 counts less than 0.4 x 10(9)/l together with inverted CD4/CD8 ratios. Such combined changes among the heterosexual and HIV-1-seronegative homosexual groups were as rare as 1.4% and 3%, respectively. For this reason, when the lymphocyte tests show less than 0.4 x 10(9)/l CD4 count and a CD4/CD8 ratio of less than unity, the individuals need to be investigated further for chronicity of this disorder, the signs of viral infections such as HIV-1 and other causes of immunodeficiency.

Adolescent↗
PubMed1992

The cumulative risk of AIDS as the CD4 lymphocyte count declines.

A method is proposed for assessing the cumulative risk of various AIDS-defining conditions as the CD4 lymphocyte count declines in HIV-infected individuals. The method is analogous to survival analysis but is based on the CD4 lymphocyte count rather than on time. Thus, the level to which the CD4 lymphocyte count has declined, rather than the length of time since seroconversion, is considered as an individual's survival interval. The survival interval may be censored (due to lack of follow-up) or treated as an interval to failure (if the individual develops AIDS). The Kaplan-Meier (product-limit) estimates, of the proportion of individuals developing AIDS before reaching a given low CD4 lymphocyte count, may be useful for determining when prophylactic treatment should begin.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Progression of HIV disease in a haemophilic cohort followed for 11 years and the effect of treatment.

OBJECTIVE: To describe the progression of HIV disease in a haemophilic cohort and to show the influence of treatment. DESIGN: 11 year longitudinal clinical and laboratory study. SETTING: A haemophilia centre. PATIENTS: 111 patients infected with HIV during October 1979 to July 1985. MAIN OUTCOME MEASURES: Symptoms of HIV infection, AIDs, and death. INTERVENTIONS: 26 asymptomatic patients started taking zidovudine or placebo (1000 mg/day) during November 1988 to February 1990; 10 patients with CD4+ counts of 0.2 x 10(9)/l started zidovudine 500 mg/day during January to November 1990. 35 patients used pentamidine for primary or secondary prophylaxis. RESULTS: At 11 years from seroconversion the estimated rate of progression to AIDS was 42% (95% confidence interval 27% to 57%); to symptoms 85% (75% to 95%); and to death 41% (25% to 57%). Progression to AIDS was significantly faster in patients aged 25 and over than in those aged less than 25 (relative risk 5.0 (2.4 to 10.4); p less than 0.00001) and in those with previous cytomegalovirus infection than in those not infected (relative risk 3.0 (1.4 to 6.8); p = 0.006). 16 of 27 (59%) patients with p24 antigenaemia developed AIDS compared with 17 of 84 (20%) patients without p24 antigen (p less than 0.001). The risk of progression to AIDS before 30 November 1988 in patients with CD4+ counts less than or equal to 0.2 x 10(9)/l was higher than after November 1988 (relative risk 1.9 (0.85 to 4.43); p = 0.1). For 1989 and 1990 the observed cumulative numbers of AIDS cases (among 81 patients with sufficient CD4+ counts) were 22 and 25 compared with 29 and 37 predicted from the rate of fall of CD4+ counts up to the end of 1988 (p = 0.03). CONCLUSION: Treatment seems to be reducing the progression of HIV disease in this haemophilic cohort.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Risk factors for stroke in middle aged British men.

OBJECTIVE: To determine the risk factors for stroke in a cohort representative of middle aged British men. DESIGN: Prospective study of a cohort of men followed up for eight years. SETTING: General practices in 24 towns in England, Wales, and Scotland (the British regional heart study). SUBJECTS: 7735 men aged 40-59 at screening, selected at random from one general practice in each town. MAIN OUTCOME MEASURE: Fatal and non-fatal strokes. RESULTS: 110 of the men had at least one stroke; there were four times as many non-fatal as fatal strokes. The relative risk of stroke was 12.1 in men who had high blood pressure (systolic blood pressure greater than or equal to 160 mm Hg) and were current smokers compared with normotensive, non-smoking men. Diastolic blood pressure yielded no additional information, and former cigarette smokers had the same risk as men who had never smoked. Heavy alcohol intake was associated with a relative risk of stroke of 3.8 in men without previously diagnosed cardiovascular disease. Men with pre-existing ischaemic heart disease had an increased risk of stroke, but only when left ventricular hypertrophy on electrocardiography was also present. CONCLUSIONS: Systolic blood pressure, cigarette smoking, and left ventricular hypertrophy on electrocardiography in men with pre-existing ischaemic heart disease were found to be the major risk factors for stroke in middle aged British men. Heavy alcohol intake seemed to increase the risk of stroke in men without previously diagnosed cardiovascular disease. A large proportion of strokes should be preventable by controlling blood pressure and stopping smoking.

Alcohol Drinking↗
PubMed1991

Serial CD4 lymphocyte counts and development of AIDS.

Low CD4 lymphocyte counts are associated with increased risk of progression to AIDS in human immunodeficiency virus (HIV) infection. We investigated the extent to which the timing of progression to AIDS can be explained solely in terms of decline of the CD4 lymphocyte count in 111 haemophiliacs followed for up to 11 years since infection with HIV. A median of 10 CD4 lymphocyte counts were made per patient. By applying a simple linear model for the decline in CD4 lymphocyte counts over time, we estimated the date of development of AIDS in 96 patients who had at least 5 determinations. 84% (81 of 96) of patients were correctly classified as to development of AIDS before Jan 1, 1990 (p less than 0.0001), with this model. The results suggest that differences in the time at which patients with HIV will progress to AIDS can largely be explained by differences in rates of decline of CD4 lymphocyte counts.

Acquired Immunodeficiency Syndrome↗