Showing papers by "Neil Pearce published in 1992"

Clues to cancer etiology from studies of farmers.

Abstract: This article summarizes cancer risks among farmers to clarify the magnitude of the problem and to suggest directions for future research. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain. These excesses occurred against a background of substantial deficits among farmers for total mortality and mortality from many specific diseases. The tumors vary in frequency, histology, and prognosis and do not fall into any obvious grouping. Two commonalities may be important. Several of the tumors excessive among farmers appear to be rising in the general population and are excessive among patients with naturally occurring or medically induced immunodeficiencies. Therefore epidemiologic studies on specific exposures among farmers may help explain the rising trend of certain cancers in developed countries and provide clues to mechanisms of action for environmental carcinogens.

Markers of Risk of Asthma Death or Readmission in the 12 Months Following a Hospital Admission for Asthma

Abstract: A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re-analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of a video questionnaire with the IUATLD written questionnaire for measuring asthma prevalence.

Abstract: Summary A video questionnaire (VQ) for measuring asthma prevalence in adolescents was assessed for repeatability and validity in relation to bronchial hyperresponsiveness (BHR) (PD20 ≤ 7.8 μmol methacholine). Comparison was also made with a standard, self completed written questionnaire (SQ), based on the IUATLD Bronchial Symptoms Questionnaire, which included five questions seeking comparable data to those in the VQ. Both the VQ and SQ were administered to 707 schoolchildren (13–16 years), in whom English was the primary language. One hundred and six randomly selected children subsequently underwent bronchial challenge to methacholine. Both the sensitivity and specificity for BHR were higher for a combination of three or more positive responses to the VQ (0.73 and 0.88), than to the SQ (0.63 and 0.82), although these differences were not statistically significant (P= 0.24). When administered again after a two week interval, the VQ had a significantly higher (P= 0.03) coefficient of repeatability (0.79) than the SQ (0.50). We conclude that the VQ is a valid and reliable method of determining asthma prevalence, and propose that by providing data relatively free from biases due to language, culture, literacy or interviewing techniques it may be particularly useful when comparing asthma prevalence and severity in different populations.

Increasing incidence of non-Hodgkin's lymphoma: occupational and environmental factors.

Abstract: The incidence of non-Hodgkin's lymphoma (NHL) has been increasing steadily for the last 30 years, and attention is being focused on the possible causes of this increase. Possible explanations have included the exposure to viruses, radiation, nutrition, and pesticides, and these issues are addressed by other presentations in this workshop. The interest in a possible role of pesticides stems from the observation that farmers have an increased risk of NHL. However, farmers may also be exposed to oncogenic viruses carried by farm animals, and studies of abattoir workers and meat inspectors have found increased risks of NHL; although these findings are unlikely to be directly relevant to the general population, they do complement other suggestions that exposure to oncogenic viruses may be a factor in the general increase in NHL. Farmers may also be exposed to chronic antigenic stimulation which may increase the risk of NHL. This latter observation is consistent with the observation that NHL is associated with several autoimmune diseases which involve chronic antigenic stimulation. NHL has also been associated with a number of occupational exposures but these are generally rare and the findings are inconsistent, although a number of studies have found an increased risk of NHL in work involving exposure to wood, solvents, or related chemicals. Perhaps the strongest evidence of an association with an environmental exposure comes from two studies showing that use of hair dyes increases the risk of NHL. This exposure is relatively common in women, and hair dye use may account for approximately 20% of all NHL cases in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of fenoterol under conditions of hypoxaemia.

Abstract: BACKGROUND: The reason for the association of increased risk of death with fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of fenoterol were enhanced by conditions of hypoxaemia.

Fenoterol and Death from Asthma in New Zealand

Abstract: This article reviews the epidemiological evidence that the use of fenoterol leads to an increased risk of death compared with other commonly used β-agonist drugs such as salbutamol, and that fenoterol

A study of New Zealand wood workers: exposure to wood dust, respiratory symptoms, and suspected cases of occupational asthma.

Abstract: A randomly selected group of 50 New Zealand wood workers was studied. The level of airborne wood dust to which they were exposed ranged from 1.0-24.5 mg/m3. The wood workers reported experiencing higher rates of both lower and upper respiratory tract symptoms than a control group of office workers. Inhaled wood dust, in particular from rimu (Dacrydium cupressinum), was frequently cited by workers as being associated with respiratory tract symptoms. The wood workers' responses to the respiratory symptom questionnaire, and serial recordings of peak expiratory flow rate were used to screen the group for suspected cases of occupational asthma. Five cases fulfilled the study's criteria for suspected occupational asthma. In four of these, further evidence was found to support this diagnosis. We conclude that exposure to wood dust may cause occupational asthma in the woodworking industry in New Zealand.

Hepatitis B vaccination in children: five year booster study.

Abstract: AIM to demonstrate that appropriate doses of hepatitis B vaccines would be protective for at least five years in children. This would be shown by administering booster doses and measuring the response. METHODS 2 micrograms intramuscular (IM) doses of Merck Sharp and Dohme (MSD) recombinant DNA vaccine (rDNAV) were given to 318 children who had received age appropriate doses of MSD plasma derived vaccine (PDV) five years earlier. Sera were tested for hepatitis B virus (HBV) seromarkers pre- and postbooster. RESULTS all children who had responsed to primary immunisation demonstrated an anamnestic response. The geometric mean titre (GMT) of antibody to hepatitis B surface antigen (antiHBs) rose from 89 to 4777 IU/L. AntiHBs was detected in 94% of vaccinees just prior to the five year booster, and 96.5% a mean of 10 days later. CONCLUSION when initial vaccine seroconversion is satisfactory, protection of responders persists for at least five years, assuming that the response to vaccine boosters mimics the response to wild virus. Therefore, for population control of hepatitis B in children in endemic areas, booster doses are not required for at least five years.

Methodological problems of time-related variables in occupational cohort studies.

Abstract: In studies of long-term health effects of occupational exposures it is important that the time patterns of the study exposure and of the relevant confounders should be taken into account in the analysis. The time-related confounders that have been most frequently considered include age at risk, calendar period, duration of employment, length of follow-up, and employment status (active or retired). These factors are related to the healthy worker effect which is more pronounced among active workers, and declines with length of follow-up. Thus, these time-related factors are potential confounders in occupational cohort studies (and in nested case-control studies). It is therefore advisable to routinely control for length of follow-up and employment status, in addition to the usual confounding factors of age at risk and calendar period. However, it should be stressed that this approach will minimise, but not eliminate, confounding due to the healthy worker effect. In particular, direct control for employment status is inadvisable if this constitutes an intermediate variable in the pathway between exposure and disease, and more complex analytical procedures are necessary in such situations. It is also important that the principle exposure under study should also be analyzed in a time-related manner, taking account of the likely induction and latency periods, and the relative etiological importance of exposure intensity, exposure duration and cumulative exposure. The simplest approach is to analyse the cumulative exposure in a time-related manner, and this may suffice when the aim is merely to consider whether or not there is an effect of exposure. However, once it has been provisionally assumed that an effect exists, attention then shifts to understanding the nature of the effect. In this context, the temporal pattern of exposure and outcome can be considered by examining the effects of exposures in specific time windows while controlling for time-related confounders, and for the effects of exposures in other time windows. A more sophisticated approach is direct fitting of a theoretical model of carcinogenesis, such as the Armitage-Doll or Moolgavkar models. However, it should be emphasized that occupational cohort studies only rarely have sufficient numbers, and data of sufficient quality, to permit meaningful conclusions to be drawn from more sophisticated analyses of this type.

Albuterol and deaths from asthma in New Zealand from 1969 to 1976: A case-control study

Abstract: It has been suggested that the association between inhaled fenoterol and deaths from asthma in New Zealand occurred because patients with unstable asthma were switched to fenoterol after its introduction in 1976. If so, a similar pattern might also have occurred after the introduction of albuterol (salbumatol) in 1969. This hypothesis has been investigated in a case-control study of 17 deaths from asthma during the period from 1969 to 1976 in patients whose ages ranged from 5 to 45 years; as in a previous study in New Zealand, two control groups were used. The inhaled albuterol odds ratio was 0.88 (95% confidence interval, 0.29 to 2.62) using control group A and 1.40 (95% confidence interval, 0.48 to 4.09) using control group B. The major problem with this study is the very small number of cases, but the findings nevertheless indicate that albuterol was not associated with deaths from asthma after its introduction. Clinical Pharmacology and Therapeutics (1992) 51, 566–571; doi:10.1038/clpt.1992.64

Asthma deaths in New Zealand: Author's reply

Abstract: raise three issues. Firstly, they suggest that the relative risk of 2-0 for fenoterol explains only a small proportion of the epidemic. Our study was based on prescribed drug treatment rather than that actually taken'; this non-differential information bias would tend to decrease the observed odds ratios towards 1.0.2 Secondly, they suggest that the epidemic could have been due to overuse of all inhaled B agonists. A similar error was recently made by Staudinger and Haas.' In fact, sales of all B agonists in New Zealand increased considerably only after 1979, three years after the onset of the epidemic,4 in response to suggestions that B agonists should be used regularly rather than on demand. The large relative risks for all B agonists in the Saskatchewan study emerged only in the questionable multivariate analysis,5 and probably tell us more about overuse of multivariate analysis than overuse of B agonists. Thirdly, they argue that mortality was declining anyway and the dramatic fall in mid-1989 is not significant, a point echoed by Jeff Garrett. Mortality declined during 1979-83 (after the epidemic was publicised) but remained relatively constant during 1983-8. Mortality remained high during the first half of 1989, whereas in the second half (after warnings about the use of fenoterol) it fell significantly (p=004) to one half of the level of the preceding six years. The analysis by Garrett seems to be based on a regression of the plotted points which does not take into account statistically the number of deaths on which each point is based. This methodological error produces absurdly wide confidence intervals that encompass the whole epidemic, and the elimination of all deaths from asthma would not be significant. Suissa and colleagues' analysis is also in error in examining yearly fluctuations which exhibit extra-Poisson variation due to non-random influences such as warning and publicity about the epidemic. Thus the time trend data are consistent with the fenoterol hypothesis (supported by four casecontrol studies' 6 7and experimental evidence8 9) but are inconsistent with the hypothesis that the epidemic was due to a class effect of all B agonists. Finally, we take exception to Garrett's claim that we have misrepresented recent mortality trends. We have presented the data in exactly the same format as used previously,' but added recent data to assess the effect of the \"natural experiment\" of warnings and restrictions on fenoterol. The other issues that Garrett raises have already been addressed in our reply'o to a similar letter\" in the New Zealand MedicalJournal. We have repeatedly found that fenoterol was not selectively prescribed to patients with more severe asthma in the population of patients with asthma recently admitted to hospital whom we studied (the situation may be different in countries like the Netherlands, where fenoterol's market share was only 23%\"). Garrett has responded to this extensive evidence by simply repeating his original claims.