Modeling the impact of changes in tobacco use on individual disease risks.

Reduced Risk Products (RRPs) do not burn tobacco and produce lower levels of toxicants than in cigarette smoke. The long-term effects of using RRPs on health are difficult to assess in a pre-market setting and a modeling approach is required to quantify harm reduction. The Population Health Impact Model (Weitkunat et al., 2015) follows a hypothetical population of individuals over time, creating their tobacco use histories and, based on these, estimating relative and absolute risks of lung cancer, ischemic heart disease, stroke and chronic obstructive pulmonary disease. Linking the tobacco use to the risk profile allow us to assess how the relative and absolute risks of these diseases vary between individuals aged 20, 30, 40 or 50 at baseline who have never smoked or who initiated smoking at 19 years old and either continued to smoke, quit smoking, or switched to RRPs with varying degrees of harm reduction. The simulations suggest that, for smokers in their 20s-30s quitting, or switching to RRP primarily prevents the accrual of risk, while in their 40s-50s it reduces risk. Though tobacco prevention has been the primary approach to limit smoking-related diseases, RRPs can also substantially reduce risks in individuals who do not quit.

Daytime sleepiness and sleep quality among Malaysian medical students.

Poor sleep quality and daytime somnolence is reported to be associated with cardiovascular events, road traffic accident, poor academic performance and psychological distress. Some studies documented that it is prevalent in most populations but its frequency among medical students has not been documented in Malaysia. This is a self-administered questionnaire survey of medical students from International Medical University, Malaysia. Daytime sleepiness of medical students was assessed using Epworth Sleepiness Scale (ESS). Student scoring ESS > 11 was regarded as having excessive daytime sleepiness. Psychological distress was measured using 12-item General Health Questionnaire (GHQ-12). A total of 799 medical students participated in this survey (response rate 69.5%). Daytime sleepiness occurred in 35.5%, psychological distress was present in 41.8% and 16.1% reported bad sleep quality. Daytime sleepiness was significantly more common among the clinical students, those with self-reported bad sleep quality and psychological distress; but unrelated to the number of hours sleep at night. We have documented high prevalence of daytime sleepiness, poor sleep quality and psychological distress. Higher frequency among clinical students and the significant relationship with psychological distress suggest possible link to the stressful clinical training.

Utilization of inpatient care and its determinants among persons with intellectual disabilities in day care centres in Taiwan.

BACKGROUND: In Taiwan, current understanding is limited concerning the manner in which health services are utilized by persons with intellectual disabilities (ID). The objective of this study is to describe the patterns of inpatient care sought by persons with ID, and factors affecting inpatient care utilization. METHOD: The primary method used in this study was a cross-sectional survey of 1390 persons with ID in day care centres. Data were obtained from responses to a questionnaire, copies of which were mailed to 30 day care centres catering for persons with ID. The questionnaire assessed demographic and health characteristics, disability status, and inpatient care utilization for the 12 months leading up to the survey. Multivariate logistic regression analysis identified factors independently associated with inpatient care. RESULTS: Findings indicated that the average age of the people with ID in the centres was 13.7 years. Fifty per cent of people were afflicted with multiple handicaps, with an average of 26 outpatient visits made per person during the 12 months, and 16% of persons having been hospitalized within the previous year. The average hospital stay was 6 days. Inpatient care was more likely to be used by those individuals with an ID who were younger, had multiple handicaps, required rehabilitation, and had other disabilities and existing illnesses. CONCLUSIONS: The study concluded that the parameters describing age of persons with ID, as having an existing illness, and requiring rehabilitative care were statistically significant in the logistic regression model of the inpatient care.

Pax6 in the sepiolid squid Euprymna scolopes: evidence for a role in eye, sensory organ and brain development.

The cloning of a Pax6 orthologue from the sepiolid squid Euprymna scolopes and its developmental expression pattern are described. The data are consistent with the presence of a single gene encoding a protein with highly conserved DNA-binding paired and homeodomains. A detailed expression analysis by in situ hybridization and immunodetection revealed Pax6 mRNA and protein with predominantly nuclear localization in the developing eye, olfactory organ, brain lobes (optic lobe, olfactory lobe, peduncle lobe, superior frontal lobe and dorsal basal lobe), arms and mantle, suggestive of a role in eye, brain, and sensory organ development.

Healthcare needs of people with intellectual disability in institutions in Taiwan: outpatient care utilization and implications.

BACKGROUND: The present study assessed the outpatient care use of people with intellectual disability (ID) in order to identify patterns of healthcare needs and the factors affecting this utilization. METHODS: The primary method used in this study was a cross-sectional survey of 1390 subjects with ID in Taiwan. Data were obtained from questionnaires completed at 30 registered institutions caring for people with ID. RESULTS: The findings show that people with ID in Taiwan are likely to make more outpatient visits per year than members of the general population. The prevalence of illness in people with ID was 41%, with epilepsy being the most frequently reported disease. A total of 39.5% of individuals with ID took medicine regularly, and 38.9% had used alternative forms of medication besides Western medicine. In terms of the use of outpatient facilities by people with ID, paediatric clinics were the most frequently utilized. The average monthly number of outpatient visits per person with ID was 2.18 (around 26 visits per year). This study found that the need for outpatient care is determined by a variety of factors relating to: the age of people with ID, the type of handicap, the place of medical treatment, having a family physician, the accessibility of medical care, the time-consuming nature of the medical visits, having an illness, ID accompanied with other disabilities, and finally, a need for rehabilitative care. CONCLUSIONS: From the examination of the expressed needs of people with ID, it was found that these individuals have a heightened need for healthcare and the treatment of special diseases/disorders in comparison to members of the general population in Taiwan. Within the context of ordinary services, it is particularly important to have a precise view of the ways in which the health needs of people with ID are different from the general population as a whole. This will enable healthcare services to respond to these needs, either through support systems within generic care or, in some cases, through the delivery of specific healthcare through specialized services which are kept separate from generic care.

Environmental tobacco smoke and cancer of sites other than the lung in adult non-smokers.

Evidence from epidemiological studies relating environmental tobacco smoke (ETS) exposure to risk of cancer of sites other than the lung in adult non-smokers is reviewed. Problems common to many studies include small sample size, inadequate control of potential confounding, failure to consider the possibility of misclassification of smoking status, reliance on death certificate diagnosis, use of proxy respondents and the possibility of recall bias. A number of the studies have other obvious weaknesses. Publication bias is known to be a problem, with two very large prospective studies having reported only very limited results. For cancers of the digestive system, bladder and brain, there is little evidence of an association with ETS exposure. Some studies have reported a relationship with cancer of the breast, cervix or nasopharynx, but the overall evidence for these sites is inconsistent and inconclusive, as is that for total cancer incidence. All three studies of nasosinus cancer have reported a statistically significant association with ETS exposure, but they are small, control poorly for potential confounding and have other weaknesses. Taken as a whole, the epidemiological evidence provides little support for the view that ETS causes cancer of any of the sites considered.

Lung cancer and type of cigarette smoked.

Lung cancer risk in smokers of different types of cigarette was compared based on evidence from 54 epidemiological studies, each of over 100 lung cancer cases. Random effects meta-analyses estimated the relative risk of lung cancer in filter and plain cigarette smokers (or with most and least filter use), in lower and higher tar smokers, in ever handrolled and manufactured only smokers, and in ever black tobacco and blond tobacco only smokers. From 43 gender-specific estimates, the risk was estimated to be 36% (95% confidence interval 27% to 44%) lower in filter than in plain cigarette smokers. The reduction was evident in both genders and in different continents. It was greater, 50% (33% to 63%, n = 11 estimates), for squamous-cell carcinoma but was also evident, 20% (-6% to 39%, n = 8), for adenocarcinoma. The risk was 23% (12% to 32%, n = 22) lower for lower tar than higher tar smokers. This reduction, seen in both genders, equates to a 2% to 3% risk reduction per milligram tar per cigarette. The risk was increased by 42% (21% to 66%, n = 15) for handrolled cigarette smoking and 75% (47% to 109%, n = 12) for black tobacco cigarette smoking. These estimates did not depend critically on results from specific studies or the limited confounding adjustment in some studies. Various problems with the epidemiological evidence are discussed, including the difficulty of obtaining compatible exposure indices from each study, the inadequate reporting of data from the largest studies, the likelihood of misreporting of cigarette type, and the inadequate control for nonsmoking confounding variables. Difficulties also arise in adjusting appropriately for aspects of smoking behavior that not only may differ between those choosing to switch or not to switch to lower tar but also may change as a result of switching. The overall data clearly show, however, that lung cancer risk is affected by the type of cigarette smoked. The suggestion that the switch to low tar cigarettes has led to an increase in the smoker/nonsmoker lung cancer relative risk and in the relative frequency of adenocarcinoma versus squamous carcinoma is shown to be weakly based. Although more data are needed relating to modern very-low-tar cigarettes, the evidence is consistent with tar reduction and the switch to filter cigarettes having reduced lung cancer risk. Indeed, the meta-analysis estimates may seriously understate the risk reductions associated with lifetime smoking of low-tar filter cigarettes.

Cumulative exposure to tamoxifen: DNA adducts and liver cancer in the rat.

Tamoxifen is a potent rat liver carcinogen, currently being used as a long-term chemopreventative for breast cancer in healthy women. The mechanism by which tamoxifen causes liver cancer in rats is known to be associated with the accumulation of tamoxifen DNA adducts in this organ. We have examined the dose-response relationship of tamoxifen-induced DNA adducts in the liver and the subsequent increase in the development of liver cancer, with and without phenobarbital promotion. Female Wistar (Han) rats were fed 420 ppm tamoxifen in the diet for 0, 1, 4, 8 or 12 weeks after which time rats were either examined immediately for hepatic tamoxifen-induced DNA damage using the 32P-Postlabelling assay, or left for lifetime for tumour assessment. A proportion of rats left for lifetime study were given phenobarbital in their drinking water. There was a clear dose-response relationship with respect to duration of tamoxifen exposure for both accumulation of DNA adducts and lifetime risk of liver cancer. In the absence of phenobarbital promotion there was a threshold value for tamoxifen-induced DNA adducts (180 adducts/10(8) nucleotides) and the subsequent induction of liver cancer. This study demonstrates the relationship between the accumulation of hepatic tamoxifen-induced DNA adducts and the development of liver cancer and establishes the threshold for hepatocarcinogenesis in terms of DNA adduct formation. These data could provide useful information in interpreting the relevance of low levels of DNA adducts in humans.

Relation between exposure to asbestos and smoking jointly and the risk of lung cancer.

OBJECTIVES: To review evidence about the joint relation of exposure to asbestos and smoking on the risk of lung cancer to answer three questions: (1) does asbestos increase risk in non-smokers; (2) are the data consistent with an additive model; and (3) are the data consistent with a multiplicative model? METHODS: Analysis of 23 studies reporting epidemiological evidence on the joint relation. Comparison of risk of lung cancer in subjects unexposed to asbestos or smoking, exposed to asbestos only, to smoking only, or to both. Estimation of the relative risk associated with asbestos exposure in non-smokers and of statistics testing for additivity and multiplicativity of risk. RESULTS: Eight of the 23 studies provided insufficient data on the risk of lung cancer in non-smokers to test for possible effects of asbestos. Asbestos exposure was associated with a significantly (p<0.05) increased risk in non-smokers in six of the remaining studies and with a moderately increased, but not significant, increase in a further six. In two of the three studies that found no increase, asbestos exposure was insufficient to increase risks in smokers. In 30 of 31 data sets analysed, risk in the combined exposure group was greater than predicted by the additive model. There was no overall departure from the multiplicative model, the proportional increase in risk of lung cancer with exposure to asbestos being estimated as 0.90 (95% confidence interval (95% CI) 0.67 to 1.20) times higher in smokers than non-smokers. For two studies significant (p<0.05) departures from a multiplicative relation were found in some, but not all, analyses. Reasons are presented why these may not indicate true model discrepancies. CONCLUSIONS: Asbestos exposure multiplies risk of lung cancer by a similar factor in non-smokers and smokers. The extent to which it multiplies risk varies between studies, no doubt depending on the type of asbestos involved, and the nature, extent, and duration of exposure.

Determination of trace elements in some natural drugs by atomic absorption spectrometry.

Fifteen kinds of common plants, animals, and minerals used as traditional medicines by the Chinese people have been subjected to analysis by atomic absorption spectrometry for its content of seven metals: lead, cadmium, arsenic, mercury, copper, cobalt, and manganese. The concentrations of these elements are significantly different according to their vegetal, animal, or mineral origin. The average values found for lead, cadmium, arsenic, cobalt, and manganese in drugs of mineral origin are higher than those derived from plants and animals, except for copper, which was higher in drugs of animal origin. Our results suggest that the user of traditional Chinese crude drugs should be warned of the potential danger of heavy-metal poisoning because their concentrations seem to be higher than the maximum values allowed by health agencies in several countries.

Accuracy of clinical diagnosis of lung cancer in Budapest in an institute specializing in chest diseases.

Among 250 consecutive autopsies (170 males and 80 females) performed at the Institute of Pulmonology in Budapest in 1996/7, there were 132 deaths in which cancer of the lung/bronchus was deemed to be the underlying cause of death. At autopsy, six cases previously thought to be dying from lung cancer were found to have died from other diseases (false positive rate = 5%). Twelve lung cancer deaths were also found to have been missed, a false negative rate of 9%, which was similar for adenocarcinoma, squamous carcinoma, and small cell carcinoma cases. Our findings confirmed the expectation expressed earlier that death certification of lung cancer would be more accurate in an institute specializing in chest diseases, to which patients had to be fit enough to be transferred, than in two general hospitals in Budapest. Nevertheless, since most cases certified as dying from lung cancer die without the benefits available in the specialized institute, the estimated false negative and positive rates for lung cancer death certification in Hungary remain high, at an estimated 56% and 30%, respectively. The much lower autopsy rates in most other countries than in Hungary points to there being considerable inaccuracy in lung cancer mortality rates internationally.

Simple methods for checking for possible errors in reported odds ratios, relative risks and confidence intervals.

Meta-analyses of data from epidemiological studies are often based on odds ratios (ORs) or relative risks (RRs) and their 95 per cent confidence intervals (CIs) as reported by the authors. Where possible ORs, RRs and CIs should be checked against the source data. Some simple methods are presented for checking the validity of reported ORs, RRs and CIs where the source data are not available. These methods include inferring the minimum total number of subjects in the study, the minimum total number of cases and the minimum number there must be in any disease/exposure category. Examples taken from the literature on environmental tobacco smoke exposure (ETS) illustrate that errors in published data are not infrequent and may stay undetected in meta-analyses.

Perceived prevalence of peanut allergy in Great Britain and its association with other atopic conditions and with peanut allergy in other household members.

BACKGROUND: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two-stage interview survey conducted in Great Britain. METHODS: A total of 16434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow-up interviews were conducted with identified sufferers from peanut allergy (stage 2). RESULTS: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%-0.55%). The prevalence in children (0.61%, 0.41%-0.82%) was slightly higher than in adults; age-of-onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree-nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. CONCLUSIONS: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to demographic factors, other food allergies, atopic conditions, and allergy in family/household members. Our study comprised a screening survey and detailed interviews with sufferers identified. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management [corrected].

Intervention studies on cancer.

This paper (and an extensive supplementary report) considers how far cancer/risk factor associations based on epidemiology have been confirmed by evidence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer markers not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 agents tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the epidemiology, while the evidence relating to calcium only concerns biomarkers. For other agents, the evidence relating to cancer itself is weak. In studies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) treatment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung cancer incidence. Studies involving pre-cancerous conditions as the endpoint, which have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and lung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyps, and that sunscreens can reduce solar keratoses. Our findings clearly show that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single dietary compounds as agents that are by themselves not responsible for the epidemiologically-observed associations between diet and cancer. However, this lack of validation must cause concern in view of the markedly conflicting evidence on beta-carotene and lung cancer between epidemiological and intervention studies. More intervention studies are needed, but in their absence, caution in interpreting epidemiological findings is warranted.

Difficulties in assessing the relationship between passive smoking and lung cancer.

Since 1981, numerous epidemiological studies have investigated the relationship between passive smoking and lung cancer in nonsmokers. The overall evidence, predominantly relating to women, indicates a weak association with the husband's smoking and many reviewers have concluded that this demonstrates a causal effect of exposure to environmental tobacco smoke (ETS). Interpreting weak associations is notoriously difficult, however, and this paper reviews problems specific to the ETS-lung cancer relationship. After describing how to select relevant studies and appropriate data, the methods for combining evidence together ('meta-analysis') are discussed, and the need to investigate sources of heterogeneity is emphasized. Separate consideration is given to various forms of bias that may affect overall relative risk estimates, including misclassification of active smoking status, confounding, systematic case-control differences, recall bias, diagnostic bias and publication bias. Sections on dose-response, multiple ETS exposure sources and other issues follow. The problems are illustrated from the available literature. It is shown there is no significant association of lung cancer with workplace, childhood or social ETS exposure or with smoking by the wife. Though statistically significant, the association with husband's smoking is weak and heterogeneous and varies widely according to various study characteristics. The association is markedly weakened by the adjustment for smoking misclassification bias and is likely to be affected by confounding and other sources of bias. While the precise extent of all the biases remains unclear, it seems impossible to conclude with any certainty that ETS causes lung cancer.