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.

Mesothelioma and the fiber type in three American asbestos factories - preliminary report.

Preliminary findings are reported from three cohort studies in two asbestos factories (A and B) where chrysotile only was processed and a third (C) where chrysotile, amosite, and crocidolite were used. A total of 10,763 men and 3,118 women has been studied, of whom 97% and 89%, respectively, have been traced and 36% and 16% have died. Death certificates have so far been obtained and coded for 89% of the deaths. The standardized mortality ratios (SMRs) for persons employed less than a year varied greatly between plants. For men employed at least 1 a, an SMR of 129 for all causes and one of 285 for respiratory cancer were found in the chrysotile textile plant (A). The experience of respiratory cancer in this textile plant appears much worse in relation to fiber exposure levels than that observed in chrysotile mines and mills. Other findings in the three plants await clarification by analyses of exposure-response relationships. Among 2,341 deaths from the two chrysotile factories there has been one mesothelioma (0.4 per 1,000); among 1,429 deaths at factory C, which used mixed fibers, there have been 18 (12.6 per 1,000). This finding supports much other evidence that amphiboles are mainly responsible for mesothelioma, whereas chrysotile has little or no mesothelioma-producing potential.

Large bowel cancer: the effect of perioperative blood transfusion on outcome.

Perioperative blood transfusion has been reported to adversely affect survival in cancer patients, but the evidence is inconclusive and may be an epiphenomenon. From the Large Bowel Cancer Project, 961 patients who underwent curative resection and left hospital alive have been reviewed to compare the effect of perioperative blood transfusion on outcome; 591 patients (61%) had been given a blood transfusion while 370 (39%) had not been transfused. Some clinical variables were equally distributed between the two groups; ie age, sex, obstruction, perforation, tumour differentiation. Three other variables known to influence patient prognosis were not equally distributed, ie tumour site, Dukes' stage and tumour mobility. Patients with tumours of the rectum and rectosigmoid, with Dukes' stage C lesions and with some degree of tumour fixation were more likely to have received blood transfusions. Using the logrank method of multivariate analysis to allow for differences in distribution of all those variables known to affect prognosis, there was no survival disadvantage for those patients who had received perioperative blood transfusion. Furthermore, there were no overall differences between the two groups of patients in their risk of developing local tumour recurrence or distant metastases. The distribution of metastases differed: in the 'transfused' group only 37% of distant metastases were found in the liver, while 71% were found in this site in the 'not transfused' group (chi 2 = 18.46, d.f. = 1, P less than 0.001). By contrast, there was a larger proportion of patients with lung metastases in the transfused group (27% vs 11%) (chi 2 = 5.59, d.f. = 1, P less than 0.05). Therefore, these data do not support the concept of an overall deleterious effect of blood transfusion on patient survival, but suggest that blood given in the perioperative period may change the biology of the metastatic process.

Smoking and health: the association between smoking behaviour, total mortality, and cardiorespiratory disease in west central Scotland.

The relationship of smoking to total mortality and to the prevalence of cardiorespiratory symptoms has been studied in three prospective surveys in west central Scotland in which 18 786 people attended a multiphasic screening examination. The prevalence of respiratory symptoms, and to a lesser extent cardiovascular symptoms, increased with the number of cigarettes smoked, with inhalation, and with a younger age of starting to smoke. A lower prevalence of respiratory symptoms in both sexes was observed in smokers of filter cigarettes than in smokers of plain cigarettes, and in those who smoked cigarettes with lower tar levels, irrespective of whether these were filtered or plain. In general, the relationships found between smoking and mortality were similar to those reported by other workers. Current cigarette smokers had a death rate from all causes which was twice that of those who had never smoked. No difference was found between the mortality rates of smokers of plain and filter cigarettes.

Population morbidity screening--practical methodology for small populations.

During a study of the health status of children in rural Nigerian communities a gross lack of fit was observed between the sample and the growth attainment standards derived from local longitudinal data. The degree of misfit was greater in children over the age of 3 years and deteriorated with age thereafter. A very high incidence of tuberculosis seemed to be responsible for the deviation in the sample. A simple practical methodology is presented, suitable for dealing with small samples: this is an application of the established Z value analysis which may easily be used by a wide variety of personnel.

Comparison of multiple puncture liquid tuberculin test with Mantoux test.

Two studies were performed to compare the disposable liquid tuberculin PPD 'Imotest' with the Mantoux test. While there was a tester effect in the first study indicating the need for accurate application of the imotest, the results of the second study showed that the two tests were comparable in selecting truly positive and negative tuberculin reactors. Results were compared both by conventional methods and by a method new to tuberculin testing, the maximum likelihood technique. This method gives a more accurate estimate of false reaction rates. A significant difference was found between reading at 48 and 72 h for both tests. The acceptability and ease of reading of the imotest, with a tuberculin selectivity comparable to the Mantoux method, make it a suitable alternative tuberculin test, especially for screening large populations.

Updating UK estimates of age, sex and period specific cumulative constant tar cigarette consumption per adult.

BACKGROUND: In 1993 we presented age and sex specific estimates of cumulative constant tar cigarette consumption (CCTCC) per adult for five year periods to 1986-90. These were derived from annual surveys conducted for the Tobacco Manufacturers' Association (TMA) since 1946, extrapolated back to 1891 for men and to 1921 for women and corrected for the decline in average (machine smoked) tar levels. We now provide estimates for 1991-5. METHODS: TMA surveys having ceased, 1991-5 estimates of manufactured cigarette consumption per adult (MCA) were derived from the General Household Survey (GHS) and corrected for the continuing decline in tar. These estimates were divided by 0.75 (men) and 0.80 (women), based on a comparison of GHS and TMA data for 1971-90, to allow accumulation with the TMA derived estimates prior to 1991. RESULTS: For both sexes the GHS/TMA ratio of MCA varied little by age or five year period, justifying the use of the correction factors when adjusting GHS estimates for 1991-95. TMA estimates were higher than GHS estimates as only TMA sales-corrected their data for understatement of smoking and the surveys differed in questions on handrolled cigarette smoking. The 1991-95 data confirm the continuing decline in CCTCC at all ages in men. Women show a less steep decline for ages 30-64 and an increase for ages 65-84. CONCLUSION: The GHS data can validly be used to update the CCTCC estimates. Some reservations about the use of CCTCC are discussed.

Trends in lung cancer, chronic obstructive lung disease, and emphysema death rates for England and Wales 1941-85 and their relation to trends in cigarette smoking.

Trends in smoking associated respiratory diseases in England and Wales during 1941-85 have been studied, with careful attention to problems caused by changes in classification of cause of death. Three diseases were selected for analysis: lung cancer, emphysema, and chronic obstructive lung disease. During 1971-85 deaths that would previously have been certified under chronic bronchitis have increasingly tended to be classified under chronic airways obstruction. The definition of chronic obstructive lung disease that was used includes both terms to avoid the artificial decline caused by consideration of chronic bronchitis in isolation. Age specific rates for all three diseases show a pronounced cohort (period of birth) pattern, rates for men rising up to the rates for those born shortly after the turn of the century and then declining, and rates for women peaking in the cohort born 20-25 years later. For chronic obstructive lung disease, but not for lung cancer and emphysema, the cohort peak is superimposed on a sharply declining downward trend. In both sexes cohort patterns of cumulative cigarette consumption peak at a time broadly similar to those seen for the three diseases. Trends in cigarette consumption, however, cannot explain the underlying steeply declining rate of chronic obstructive lung disease. Nor can they fully explain the declining trends in lung cancer and emphysema rates in younger men and women.

Prediction of outcome after curative resection for large bowel cancer.

Prospectively collected information on 2524 patients who had undergone "curative" resection for colorectal cancer was analysed to establish the rank-order of importance of both clinical and pathological factors affecting outcome. The patients were divided into two groups. In the first, a statistical weighting was established for each prognostic factor and those that influenced long-term survival were, in order of importance, lymph node status, tumour mobility, number of lymph nodes positive for tumour, presence of bowel obstruction, and depth of primary tumour penetration. Factors that influenced in-hospital mortality were cardiopulmonary complications, intraabdominal sepsis (without anastomotic leak), presence of bowel obstruction, and age. In the second group these mathematical weightings were applied, and the predicted and observed outcomes were in close agreement. Statistical techniques of this kind will be of value in prognosis and in analysis of the results of new treatment regimens.

Influence of tumour site on presentation, management and subsequent outcome in large bowel cancer.

To demonstrate any difference in outcome between patients with carcinoma at various sites within the large bowel, analysis of a large number of patients is necessary. From the Large Bowel Cancer Project, 4292 patients have been evaluated to compare mode of presentation, surgical management, pathological findings and outcome. Carcinoma at the splenic flexure was associated with the highest risk of obstruction (49 per cent); postoperative cardiopulmonary complications (36 per cent); in-hospital mortality (18 per cent); and the lowest age-adjusted 5-year survival (28 per cent), even after curative resection (38 per cent). This survival disadvantage was seen even in those without obstruction. Further, it was not accounted for by differences in age, sex, Dukes' stage or tumour differentiation between the various sites as stratification by these variables failed to alter significance (log rank chi 2 = 11.1; d.f. = 4; P less than 0.05). Compared with carcinoma of the left colon and rectum, tumours in the right colon were more likely to be poorly differentiated and locally advanced (in terms of fixation and penetration of the bowel wall) but were not associated with a higher risk of either distant spread at presentation or local recurrence. Age-adjusted 5-year survival following curative surgery was higher for the right colon (65 per cent) than the left (59 per cent).

Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma.

About half the patients treated with curative resection for colorectal cancer do not survive long-term. Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival. In patients with colorectal cancer, we have done a multicentre, randomised controlled trial comparing five-year survival after intraportal infusion of fluorouracil (1 g per day) plus heparin (10,000 U per day) (130 patients) or heparin alone (123) during curative resection and for 7 days thereafter, or after resection alone (145). There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study. However, patients who had stage III, Dukes' C (lymph-node-positive) tumours resected and were treated with fluorouracil plus heparin had a significant (p less than 0.03) survival advantage of about 16% compared with surgery-only controls. Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile.

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].

Dust exposure and mortality in an American chrysotile textile plant.

Three parallel cohort studies of asbestos factory workers were undertaken to investigate the effects of mineral fibre type and industrial process on malignant mesothelioma, respiratory cancer, and asbestosis. This report describes the mortality of a cohort of 2543 men, defined as all those employed for at least a month from 1938 to 1958 in a textile plant in South Carolina in which chrysotile was the only type of asbestos used. Of these, 863 men (34%) had died before 31 December 1977, one from malignant mesothelioma. Twenty one deaths were ascribed to asbestosis and 66 to cancer of the lung. Compared with the number expected from South Carolina, there was an excess of 30 deaths from respiratory cancer (ICD 160-164) in men 20 or more years after first employment (SMR 199.5). In men employed five years or more, no SMRs for this category rose above 300. Individual exposures were estimated (in mpcf X years) from recorded environmental measurements. Life table analyses and "log-rank" (case-control) analyses both showed a steep linear exposure-response that was some 50-fold greater at similar accumulated dust exposures than in Canadian chrysotile mining and milling. These findings agree closely with those from another study in this plant and confirm that mesothelioma is rarely associated with chrysotile exposure. Cigarette smoking habits did not greatly differ between the textile workers and the Canadian miners and millers. The far greater risk of lung cancer in the textile industry, if not attributable to other identified cocarcinogens, may be related to major differences in the size distribution of fibres in the submicroscopic range which are not detected by the usual fibre or particle counting procedures.

Dust exposure and mortality in an American factory using chrysotile, amosite, and crocidolite in mainly textile manufacture.

This report describes the second in a series of three parallel cohort studies of asbestos factories in South Carolina, Pennsylvania, and Connecticut to assess the effects of mineral fibre type and industrial process on mortality from malignant mesothelioma, respiratory cancer, and asbestosis. In the present plant (in Pennsylvania) mainly chrysotile, with some amosite and a small amount of crocidolite, were used primarily in textile manufacture. Of a cohort of 4137 men comprising all those employed 1938-59 for at least a month, 97% were traced. By the end of 1974, 1400 (35%) had died, 74 from asbestosis and 70 from lung cancer. Mesothelioma was mentioned on the certificate in 14 deaths mostly coded to other causes. All these deaths occurred after 1959, and there were indications that additional cases of mesothelioma may have gone unrecognised, especially before that date. The exposure for each man was estimated in terms of duration and dust concentration in millions of dust particles per cubic foot (mpcf) from available measurements. Analyses were made both by life table and case referent methods. The standardised mortality ratio for respiratory cancer for the whole cohort was 105.0, but the risk rose linearly from 66.9 for men with less than 10 mpcf.y to 416.1 for those with 80 mpcf.y or more. Lines fitted to relative risks derived from SMRs in this and the textile plant studied in South Carolina were almost identical in slope. This was confirmed by case referent analysis. These findings support the conclusion from the South Carolina study that the risk of lung cancer in textile processing is very much greater than in chrysotile production and probably than in the friction products industry. The much greater risk of mesothelioma from exposure to processes in which even quite small quantities of amphiboles were used was also confirmed.

Malignant large bowel obstruction.

Of 4583 patients in the Large Bowel Cancer Project, 713 (16 per cent) were obstructed. The site of greatest risk was the splenic flexure (49 per cent). Advanced stage was neither the full reason why some patients obstructed nor for their subsequent poor prospects (age-adjusted 5-year survival: not obstructed, 45 per cent; obstructed, 25 per cent). Also, there was no greater risk of vascular invasion, no heavier lymph node burden and no worse tumour differentiation in patients with obstruction. In-hospital mortality was high (23 per cent), was not reduced by either a policy of primary or staged resection and was not influenced by the site of obstruction. There was no survival advantage for either policy, but hospital stay after primary resection was half that of staged. Immediate anastomosis in the obstructed left colon had a high clinical leak rate (18 per cent versus 6 per cent elective; P less than 0.001). Both registrars and consultants had similar mortality rates for elective primary resection and for the management of obstruction itself (as evidenced by results after the first stage of a staged resection). Selection probably accounts for the very much better results achieved by consultants for primary resection in the presence of obstruction (in-hospital mortality: consultants, 13 per cent; registrars, 24 per cent).

Local recurrence following 'curative' surgery for large bowel cancer: II. The rectum and rectosigmoid.

1988 patients with an adenocarcinoma of the rectum (1292; 65 per cent) or rectosigmoid (696; 35 per cent) have been studied. A resection (1700 patients) or polypectomy (124 patients) was performed in 1824 (92 per cent) and, of the former, 1376 patients either underwent abdominoperineal (AP) excision of the rectum (788 patients) or an anterior resection (598 patients). The in-hospital mortality was 63 patients (8 per cent) for AP and 44 (7 per cent) for anterior resection, and a curative resection had been performed in 504 (71 per cent) of those undergoing an AP, and 393 (71 per cent) of those undergoing an anterior resection. Follow-up information is available for 478 patients (95 per cent) who underwent an AP and 370 (94 per cent) who underwent an anterior resection. More patients have developed a local recurrence after an anterior resection (67; 18 per cent) than after AP (57; 12 per cent) (Logrank chi2 = 6.6, d.f. = 1, P less than 0.02) (stratified for sex and Dukes' stage). This difference is not accounted for by a lesser margin of distal clearance after an anterior resection; firstly because the margin of clearance was not different in those who did and those who did not develop a local recurrence (AP: whole group = 4.4 cm, local recurrence = 4.5 cm; anterior resection: whole group = 3.0 cm, local recurrence = 3.1 cm) and secondly because for each centimetre of distal clearance there was a consistently greater probability of recurrence for anterior resection (Logrank chi2 = 9.1, d.f. = 1, P less than 0.01) (stratified for sex, Dukes' stage and distal clearance margin).

Local recurrence following 'curative' surgery for large bowel cancer: I. The overall picture.

The Large Bowel Cancer Project is a collaborative prospective study of 4228 patients with a histologically proven adenocarcinoma, of whom 2336 (55 per cent) survived a 'curative' resection. Follow-up information is available on 2220 patients (95 per cent). Subsequently, 309 (14 per cent) have developed a local recurrence confirmed by: biopsy (127; 41 per cent), clinical examination (77; 25 per cent), X-ray (15; 5 per cent), a raised CEA (2; 1 per cent), or some other method - e.g. CT scan or a confident unbiopsied laparotomy finding (88; 29 per cent). Statistically significant factors (chi2 test, P less than 0.05) associated with local recurrence are: Dukes' classification: A 4 per cent; B 13 per cent; C 18 per cent Tumour differentiation: Well 11 per cent; Moderate 14 per cent; Poor 21 per cent Obstruction: Absent 13 per cent; Present 21 per cent Perforation: Absent 13 per cent; Present 28 per cent Tumour mobility: Freely mobile 11 per cent; Others 21 per cent Operation performed (rectal and rectosigmoid tumours): Abdomino-perineal 12 per cent; Anterior resection 18 per cent; Surgeon (Consultant only): Range less than 5 per cent to greater than 20 per cent. Stratification of the above variables altered only the statistical significance pertaining to tumour differentiation (P less than 0.1, d.f. = 2). In particular, the differences between Consultant surgeons remained.

Large bowel cancer: surgical pathology and its relationship to survival.

Modifications of Dukes' (1932) classification of rectal tumours have led to confusion. From the data of 2518 patients who had undergone curative colorectal surgery the interrelationships between tumour penetration, grade, vascular invasion and pattern of lymph node involvement have been examined and their individual relevance to survival determined. Subdivision of Dukes' A cases into those confined to the muscularis mucosae (A) and those penetrating into, but not through, the bowel wall (B1) should be abandoned. Despite interrelationships between lymph node status, grade of tumour and vascular invasion, they all contribute prognostic information independent of each other. Apical lymph node involvement, more than four lymph nodes involved and extensive primary tumours with nodal involvement all carry a bad prognosis. Although interrelated each variable is individually relevant. However, subgroups of patients with Dukes' C tumours have an observed survival significantly better than expected. When few lymph nodes are involved or the primary tumour is confined to the bowel wall but lymph nodes are involved, the expectation of life is equivalent to Dukes' B.

Dust exposure and mortality in an American chrysotile asbestos friction products plant.

Cohort studies in three American asbestos factories were undertaken to investigate the effect of fibre type and manufacturing process on lung cancer, mesothelioma, and asbestosis. Reports have been published on a chrysotile textile plant in South Carolina and a mainly textile plant in Pennsylvania, which also used amphiboles. In the third plant in Connecticut friction products and packings were made from chrysotile only. In a cohort of 3641 men employed for one month or more, 1938-58, 3513 (96.5%) were traced, 1267 (36%) had died, and death certificates were obtained for 1228 (96.9%). Individual exposures were estimated (in mcpf . years) from impinger measurements. Life table analyses using Connecticut mortality rates gave an SMR for all causes of 108.5 (USA 107.9). The SMR (all causes) for men who had worked for less than a year was 129.9 and for those who had worked for a year or more, 101.2. The equivalent SMRs for respiratory cancer were 167.4 and 136.7 respectively. Excluding men who had worked for less than a year, there was possible evidence of some increase in risk of lung cancer with increasing exposure, supported also by a "log-rank" (case-control) analysis, of the same order as that observed in chrysotile mining and milling. These findings may be compared with chrysotile textile manufacture where the risk of lung cancer was some 50-fold greater. It is suggested that the differences in risk are perhaps related to the higher proportion of submicroscopic fibres in textile manufacture that may result from the traumatic carding , spinning, and weaving processes. No case of mesothelioma was found, consistent with a much lower risk of this tumour with chrysotile than with amphiboles. Twelve deaths (nine in men with very short and low asbestos exposure) were given ICD code 523 (pneumoconiosis); all but two were ascribed to anthracosilicosis or silicosis and none to asbestosis.

Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis.

A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten-free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life.