Search

The dramatic increase during the past decade in prostate-specific antigen (PSA) testing and prostate biopsies has resulted in the detection of large numbers of small lesions, an increase in the incidence of prostate cancer, and an increasing incidence-to-mortality ratio. Currently, the risk of being diagnosed with prostate cancer is increasingly greater than the risk of dying of it. The currently available treatments for prostate cancer are not well suited to treating small or indolent tumors. Radical treatment, whether surgery or radiotherapy, can eradicate cancer effectively, but these techniques, as well as hormonal manipulations, can have adverse effects on patients' health and quality of life. Watchful waiting, or “active surveillance,” has the advantage of avoiding the deleterious effects on quality of life, but it confronts patients with the emotional burden of living with an untreated cancer that could progress and metastasize. For active surveillance, no established, objective criteria are available for progression that would signal the optimal time for therapeutic intervention. PSA levels in patients with low-risk, small-volume cancers are more indicative of the size of the benign prostate or the presence of inflammation than of changes in the volume or growth of the cancer, and PSA levels inherently fluctuate, creating a low signal-to-noise ratio until the cancer is very large. Little risk exists in waiting to confirm a sustained increase in the PSA level before proceeding with a diagnostic biopsy. This policy would decrease the number of unnecessary biopsies, but still diagnose men within a safe timeframe. In studies controlled for age and comorbidity, the survival rate for patients with low-risk prostate cancer mirrors that expected in the general population. This holds true across cohorts of patients, whatever the treatment used. Because no strong medical or scientific evidence supports any particular ablative technique for low-risk prostate cancer, no standard of care has been universally accepted. Therefore, practice patterns are heterogeneous and depend more on the availability of treatments than on the features of the disease itself.

Epidemiological studies show that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer incidence. We measured the rate ratio for colorectal adenocarcinoma according to dosage and the timing of exposure by means of a case–control study, nested in a non-concurrent cohort linkage study, using the population of beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 as the source population. Four controls per case, matched on age and gender and alive when the case was diagnosed, were randomly selected. Dispensing rates, calculated over successive time periods, characterized NSAID exposure. We accrued 3844 cases of colon cancer and 1971 cases of rectal cancer. For colon cancer a significant trend towards a decreasing rate ratio was associated with increasing exposure during the 6 months preceding diagnosis (P-trend = 0.002). For both cancers, significant trends were associated with exposure 11–15 years before diagnosis (colon: P-trend = 0.01; rectum: P-trend = 0.0001). At the highest exposure levels the rate ratio for colon cancer was 0.57 (95% confidence interval (CI) 0.36–0.89); for rectal cancer it was 0.26 (95% CI 0.11–0.61). No protection was associated with exposure during other periods. The timing of NSAID use must be considered in planning intervention trials to prevent colorectal cancer. There may be a 10-year delay before any preventive effect will appear. © 1999 Cancer Research Campaign

Past experience with a drug may modify the risk of adverse event associated with current use of this drug. This effect was investigated empirically with a study on non-steroidal anti-inflammatory drugs (NSAIDs)-gastropathy. A hospital-based case-control study was conducted with 244 cases of upper gastrointestinal bleeding (UGIB) age 68 and over and 615 matched controls. Data on all medications dispensed to the study patients during the 3 years preceding admission were obtained from the Quebec universal prescription program automated database. Recent use (within 30 days prior to admission) of non-aspirin NSAIDs increased the risk of UGIB. The estimate of relative risk (RR) was 3.4 (CI, 2.1-5.5). Use of NSAIDs in the previous 3 years was associated with a lower risk of UGIB; the estimate of RR was 0.7 (CI, 0.4-1.0). The estimate of RR for first-time users was 22.7 (2.8-200.0) vs 3.0 (1.9-4.7) for those who had used the drugs at least once in the past 3 years. These results provide empirical evidence of a depletion of susceptibles effect whereby patients who remain on the drugs are those who can tolerate them while those who are susceptible select themselves out of the population at risk. Thus, past use should be considered as a potential risk modifier in non-experimental risk assessment of events associated with drug use.

Purpose - The objective of this study was an evaluation of the sensitivity of findings of the relationship between oral corticosteroid use and the risk of fracture. We found in earlier work that the risk of fracture was significantly higher during oral corticosteroid treatment, with increases of 61% in hip and 160% in vertebral fractures.Methods - Information was obtained from the General Practice Research Database which contains medical records of general practitioners in the UK. The study included 244,235 oral corticosteroid users and 244,235 controls.Results - The validation of fracture cases showed that the hip fractures, as recorded in the GPRD, were confirmed by the GP on the questionnaire in 90.7% of the cases and by discharge summary in 86.5%. The relative rate of non-vertebral fracture during oral corticosteroid use did not vary substantially between patients with different diseases, age, or gender. The sensitivity analysis, modifying the type of analysis or inclusion of patients, did not materially change the findings.Conclusions - We found a high level of validity of the GPRD with respect to hip and vertebral fractures. The sensitivity analysis indicated internal validity and consistency of the findings on fracture risks of oral corticosteroid therapy. Copyright (c) 2000 John WileySons, Ltd.

Interest in focal therapy for prostate cancer has recently been renewed owing to downward stage migration, improved biopsy and imaging techniques, and the prevalence of either unifocal cancer or a dominant cancer with secondary tumors of minimal malignant potential. Several techniques have potential for focal ablation of prostate cancer. Cryotherapy has been used for some time as primary therapy for complete ablation of the prostate or local recurrence after radiotherapy. Enthusiasm for cryotherapy as the primary therapy has been tempered by the uncertainty about complete ablation of the cancer, the frequent persistence of measurable prostate-specific antigen levels after the procedure, and a high rate of erectile dysfunction. Studies have reported "focal ablation" of prostate cancer with cryotherapy, targeting 1 side of the gland to eliminate a cancer confined to that side with less risk of urinary or sexual complications. Whether cryotherapy has sufficient power to eradicate focal cancer and can be targeted with sufficient accuracy to avoid damage to surrounding structures remains to be demonstrated in prospective clinical trials. High-intensity focused ultrasound (HIFU) has been used widely in Europe for complete ablation of the prostate, especially in elderly men who are unwilling or unable to undergo radical therapy. For low- or intermediate-risk cancer, the short- and intermediate-term oncologic results have been acceptable but need confirmation in prospective multicenter trials presently underway. Whole gland therapy with transrectal ultrasound guidance has been associated with a high risk of acute urinary symptoms, often requiring transurethral resection before or after HIFU. Adverse effects on erectile function seem likely after a therapy that depends on heat to eradicate the cancer, but erectile function after HIFU has not been adequately documented with patient-reported questionnaires. HIFU holds promise for focal ablation of prostate cancer. As with cryotherapy, focal HIFU should reduce the adverse sexual, urinary, and bowel effects of whole gland ablation. New techniques are being developed to allow HIFU treatment under real-time guidance using magnetic resonance imaging, which could improve the precision and reduce the adverse effects further. Another promising technique, currently in clinical trials, is vascular-targeted photodynamic therapy, which has been used for whole gland ablation of locally recurrent cancer after radiotherapy and, more recently, for focal ablation of previously untreated cancer. In combination with a new, systemically administered photodynamic agent, laser light is delivered through fibers introduced into the prostate under ultrasound guidance. This technique does not heat the prostate but destroys the endothelial cells and cancer by activating the photodynamic agent. Damage to surrounding structures appears to be limited and can be controlled by the duration and intensity of the light. We have reviewed the principles of focal therapy and these new therapeutic modalities.

This article relates the experiences of the exceptional heat wave of the summer 2003 in France to heat related events as a whole. It focuses on five issues: first, whether heat-waves should be considered as epidemics or as endemic events in order to achieve efficient mitigating strategies. It is recommended to consider heat-waves as both, although it is clear that epidemic situations cannot be dealt with properly without a more general program to decrease the effects of endemic heat-related ill health. Second, it is stressed that there is no model available for predicting the occurrence of future epidemics with the required sensitivity and specificity: More detailed analysis has to be carried out. In addition, it is recommended that the threshold for future relief actions be lowered. Third, the issue of what surveillance system is required to detect epidemics of heat-related illnessis addressed. Fourth, the efficacy and effectiveness of prevention plans are briefly evaluated as well as what must be done during epidemics. Finally, the relationship between epidemics and polical crises is outlined.

Summary. Background: It is not known whether burden-of-illness differs in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. Objective: To compare severity of disease and quality of life in chronic venous disease patients with and without prior venous thromboembolism. Patients and methods: The VEINES Study population is an international cohort of 1531 outpatients with chronic venous disease in Belgium, France, Italy and Canada. Clinical severity of chronic venous disease graded using the seven-category ‘CEAP’ scale, and quality of life using standardized generic (SF-36) and venous disease-specific (VEINES-QOL/Sym) questionnaires were compared in patients with and without venous thromboembolism. Multivariable analyses with adjustment for known confounders were used to examine associations between venous thromboembolism and quality of life. Results: One hundred and fifty-one (10%) patients had prior venous thromboembolism. These patients had more severe chronic venous disease than those without venous thromboembolism (P

Exogenous substances such as the appetite suppressant fenfluramine are known to be causally related to the development of pulmonary arterial hypertension (PAH). In these cases, the clinical course as well as the pulmonary vascular disease pathologically is indistinguishable from idiopathic PAH. Other exogenous substances, such as amphetamines, cocaine, and meta-amphetamines, have been considered to be potential risk factors for inducing PAH. SOPHIA (the study of pulmonary hypertension in America), in addition to confirming previous reports of a causal association between the appetite suppressant fenfluramine and PAH, unexpectedly found a significantly increased risk for the development of PAH with exposure to over-the-counter antiobesity agents containing phenylpropanolamine. The first case is reported of fatal PAH in a child heavily treated with cold remedies containing phenylpropanolamine, which, in addition to the results of SOPHIA, strengthens the hypothesis that phenylpropanolamine is a risk factor for the development of PAH.

Estrogen has been found to increase the risk of deep vein thrombosis (DVT), which is associated with venous ulcers. A matched case-control study was therefore performed to quantify the effect of hormone replacement therapy (HRT) on the occurrence of venous ulcers of the lower limbs.Women presenting to a participating vascular surgery department between January and December 1997 with a first open venous ulcer served as cases. Controls were sampled among women with sub-acute conditions such as skin problems, cold, headache/migraine, sore throat and mild ear infections, and were matched on referral site and age (+/- 5 years). Subjects were eligible for this study if they were postmenopausal, and excluded if they had non-palpable pedal pulse or any chronic active diseases. The study consisted of an interviewer-administered risk factor questionnaire. Conditional multivariate logistic regression analyses were performed adjusting for history of DVT and unbalanced distributions in important covariates.Forty-four cases and 80 matched controls were recruited. The mean age of participants was 64 years. HRT users were significantly thinner (27% with body mass index (BMI = (kg/height (m2))or = 27 vs. 41%, p = 0.04) and less likely to have a history of DVT (12 vs. 33%, p = 0.02) and varicose veins (VV) (52 vs. 69%, p = 0.04) than non-users. A matched univariate logistic regression analysis was performed to quantify the effect of HRT on venous ulcers and generated an odds ratio (OR) of 0.14 with 95% confidence interval of (0.04, 0.49)95%: adjusting for prior DVT resulted in an OR of 0.29 (0.09, 0.93)95%. When adjusting for BMI, history of VV, exercise, education, and smoking, the OR observed was 0.03 (0.01, 0.13)95%: further adjustment for prior DVT gave an OR estimate of 0.06 (0.01, 0.50)95%CI.Our study demonstrates that HRT has a protective effect on the occurrence of venous ulcers of the lower limbs. Adjusting for prior DVT moves the estimate closer to the null. DVT is a strong contraindication for HRT and therefore must be considered in order to eliminate confounding by contraindication.

The objective of this study was to estimate the number of fractures attributed to oral corticosteroid use.Information was obtained from the General Practice Research Database which contains medical records of general practitioners in the UK. The total number of corticosteroid-related fractures during a course of treatment was estimated using the formula for attributable risk among the exposed.A total of 244 235 patients was prescribed an oral corticosteroid. The rate of hip fractures increased exponentially with age in both males and females. The excess number of hip fracture cases among females aged 85 years or older using 7.5 mg prednisolone per day or more was 1.4 cases per 100 patients per year. About 47% of all hip and 72% of all vertebral fractures that occurred can be attributed to oral corticosteroid use. Among 10 000 female users of higher doses, 99.7 nonvertebral, 31.6 hip and 45.8 vertebral fractures can be attributed to use of oral corticosteroids.The targeting of high-risk patients will be important for implementing preventative strategies in a cost-effective manner.

Although many clinicians believe high growth leads to inflexibility, which may lead to lower extremity pain, the only prospective data suggest growth is unrelated to flexibility. However, it is still possible that growth and/or flexibility are related to pain even if they are not related to each other. We investigated the incidence of leg pain in adolescents to determine whether high growth spurt and/or poor flexibility are risk factors for the development of lower extremity pain.Repeated measures, prospective cohort study of urban high school students aged 12-18. Subjects were measured at baseline and at 6 and 12 months for flexibility of hamstrings and quadriceps and with the sit-and-reach test. Participants completed a detailed questionnaire on recreational activity, occupational activities, psychosocial variables, and musculoskeletal pain.Poor hamstring flexibility (odds ratio 0.99, confidence interval 0.97-1.01), poor quadriceps flexibility (OR 1.01, CI 0.99-1.03), poor sit-and-reach flexibility (OR 0.99, CI 0.99-1.01), and growth (OR 0.93, CI 0.50-1.71) were not related to the development of lower extremity pain. There was an association between lower extremity pain and occupational activities (OR 2.08, CI 1.45-2.98) and poor mental health (per 1 SD change, OR 1.41, CI 1.19-1.67).Neither growth nor flexibility is related to the development of lower extremity pain in adolescents. A poor mental health score and occupational activities may be associated with the development of lower extremity pain.

In France, the health and solidarity department of Employment and solidarity Ministry have just been re-organised. The Directory General of the department of Health is experiencing a complete revision of its functions and organisation. This article presents the public health context which has been taken into account for this new organisation and explains its main principles and strategic orientations. The new organisation chart is clarified. It is made up by two departments and seven under-directions. Up to now, control and administrative supervision were predominant among Health General Direction functions. They are now oriented to administrate missions prioritizing the function of health doctrines' elaboration, of programmation, animation and coordination. As the guarantor of sanitary security, the Health General Direction has also to impulse a new partnership which does not only include health professional, social and health organisation and the economic actors: citizen in general and service users in particular have to be included to promote health democracy.

The international study of insulin and cancer. Grimaldi-Bensouda L, Marty M, Pollak M, Cameron D, Riddle M, Charbonnel B, Barnett AH, Boffetta P, Boivin JF, Evans M, Rossignol M, Benichou J, Abenhaim L; ISICA group.

To critically review the classification, epidemiology, outcomes, diagnosis and treatment of chronic venous disorders of the leg (CVDL), to issue evidence-based recommendations, and to identify areas requiring further research.Articles identified by an extensive literature search were scored by members of an international task force. Only those articles with a moderate or strong rating for internal validity were retained.A scoring system weighing CVDL severity according to the probability of ulcer occurrence is proposed. Epidemiological data on the frequency of CVDL and its risk factors are reviewed. The following items are evaluated: costs associated with treatment; clinical outcomes related to CVDL and its treatment; available generic and disease-specific measures of quality of life; diagnostic procedures used to detect venous reflux; and efficacy of available treatments.CVDL is an important public health problem, based on its prevalence, cost and impact on quality of life. High-priority areas for research on CVDL are identified.

Symptoms and clinical signs individually are inaccurate for the diagnosis of DVT. However, when assessing patients with leg symptoms, clinicians have access to additional information, such as whether or not DVT risk factors are present that could improve the accuracy of clinical judgment. The purpose of this study was to identify which clinical variables best predict DVT, and to use these variables to create a clinical prediction index for DVT. We studied 271 university hospital patients with a first episode of symptomatic, clinically suspected DVT. The prevalence of DVT was 27%, of which 71% were proximal. At baseline, information was collected on demographic features, comorbidity, and symptoms and signs. A Bayesian model selection strategy was used to estimate the logistic regression model that best predicted DVT. Male sex [OR = 2.8 (1.5, 5.1)], orthopedic surgery [OR = 5.4 (2.2, 13.6)], warmth [OR = 2.1 (1.2, 3.9)] and superficial venous dilation on exam [OR = 2.9 (1.4, 5.7)] were independent predictors of DVT. Using the model, a clinical prediction index that categorized patients into different levels of DVT risk was created, and was useful in a theoretical strategy aimed to limit the need for contrast venography in patients with suspected DVT, such that 96% of study patients could have avoided contrast venography. This index should be evaluated prospectively in other patient populations.

The objective of this study was to evaluate the inter-rater reliability of the Leg-O-Meter, an instrument designed to measure the ankle or calf circumference. The Leg-O-Meter consists of a tape measure fixed to a stand attached to a small board on which the patient is in standing position. For this study the tape measure of the Leg-O-Meter was fixed at 10 cm from the board in order to standardize all measurements. Informed consent to participate in the study was obtained from 39 patients consulting the phlebology clinic of Hôpital St-Michel, Paris, France. Participants were asked to enter a closed room where four independent and blinded observers consecutively took measurements of both legs with the Leg-O-Meter. The order of the observers was randomized between patients. Under the assumption of a two-way random effects model an intraclass correlation coefficient (ICC) was used to determine the reliability or reproducibility of a measure with the Leg-O-Meter. The overall reliability coefficient calculated by the ICC for the right and left leg were estimated at 97.09% [95.52%;100%]95% and 97.08% [95.86%;100%]95%, respectively. The authors conclude that the Leg-O-Meter gives a standardized and reliable measure of the circumference of the ankle. Furthermore, it is not invasive or costly.

Recently, a cluster of patients was observed in France in whom primary pulmonary hypertension developed in patients exposed to derivatives of fenfluramine in appetite suppressants (anorexic agents), which are used for weight control. We investigated the potential role of anorexic agents and other suspected risk factors for primary pulmonary hypertension.In a case-control study, we assessed 95 patients with primary pulmonary hypertension from 35 centers in France, Belgium, the United Kingdom, and the Netherlands and 355 controls recruited from general practices and matched to the patients' sex and age.The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension (odds ratio with any anorexic-drug use, 6.3; 95 percent confidence interval, 3.0 to 13.2). For the use of anorexic agents in the preceding year, the odds ratio was 10.1 (95 percent confidence interval, 3.4 to 29.9). When anorexic drugs were used to a total of more than three months, the odds ratio was 23.1 (95 percent confidence interval, 6.9 to 77.7). We also confirmed an association with several previously identified risk factors: a family history of pulmonary hypertension, infection with the human immunodeficiency virus, cirrhosis, and use of cocaine or intravenous drugs.The use of anorexic drugs was associated with the development of primary pulmonary hypertension. Active surveillance for this disease should be considered, particularly since their use is expected to increase in the near future.

The surveillance of individual and aggregate patterns of prescribed medication can potentially provide some very useful information to those involved in public health. At present however, this activity has attracted relatively little attention in Canada. This article will introduce a conceptual framework with which to examine the possibilities of prescription drug monitoring as a tool for public health surveillance. The sources of data available to undertake this activity as well as their limitations, will be presented along with some recent concrete applications.

Manipulative therapy has been one of the most intensively studied approaches to back pain management. This paper reviews 20 years of randomized clinical trials of manipulative therapy, and addresses the following issues: for what condition were these patients treated? What was the population studied, and were workers included? Was a specific technique, spinal manipulation, or a more global approach the object of the trial? Finally, were there long-term outcome measures? The 21 randomized clinical trials reviewed here provide some indication that manipulative therapy offers some positive short-term results; it is not clear at this point whether long-term effects of the treatment have been adequately evaluated. Lack of specificity in the description of samples makes it impossible to conclude on the benefit of spinal manipulation for workers. Whether manipulation is solely responsible for the changes mentioned in these studies, independently of the global approach put forth by its practitioners, is also an open question that awaits further study.

Introduction La cohorte FDRK est une cohorte de patients atteints de cancer colorectal dont l’objectif est de decrire la prise en charge des patients et leur devenir sur un an. La methode de l’etude, les caracteristiques des patients a l’inclusion sont presentees. Patients et Methodes Parmi les centres prenant en charge le cancer du colon en France, un echantillon aleatoire tenant compte de la taille et du type d’etablissement a ete identifie. Les criteres d’inclusion des patients etaient les suivants : âge de 18 ans et plus, diagnostic d’adenocarcinome primitif du colon ou du haut rectum avec confirmation histologique du diagnostic inferieure a 3 mois. Les donnees ont ete recueillies prospectivement par les medecins participants et/ ou a partir des dossiers medicaux. Resultats Entre juin 2006 et avril 2008, 1 076 patients ont ete inclus dans l’etude par 96 centres. Les 96 centres participants etaient distribues en : 37 % de centres prives, 35 % d’hopitaux generaux et 27 % de centres hospitaliers universitaires. Les services participants etaient des services d’hepato-gastroenterologie (38 %), de chirurgie (33 %) ou d’oncologie (25 %). Les patients inclus etaient majoritairement des hommes (55,3 %) et l’âge median etait de 69,2 ans. Les modes de decouverte du cancer etaient des symptomes digestifs (63,6 %), des complications digestives (15,9 %), une anemie (16,8 %), une coloscopie de surveillance et/ou de depistage (17,5 %) ; 12,6 % des patients avaient au moins un parent du premier degre atteint d’une tumeur colorectale. Les stades etaient : in situ 2 %, stade I 9 %, stade II 28 %, stade III 35 %, stade IV 25 %. Les patients avec un cancer non metastatique etaient plus frequemment operes que ceux avec un cancer metastatique (92 versus 71 %). Au moment de l’analyse, parmi les patients qui avaient recu une chimiotherapie, les informations sur le traitement etaient disponibles pour 90 % des patients non metastatiques et 77 % pour ceux avec metastases. Un traitement adjuvant a ete administre a 38,3 % de stade II et 68,9 % de stade III. Ce traitement etait du FOLFOX dans 67,6 % des cas (57 % non simplifie et 43 % simplifie). 74,7 % des patients presentant un cancer metastatique ont recu une chimiotherapie a base de fluoropyrimides (± oxaliplatine ou CPT11) avec du bevacizumab dans 39 % des cas. Conclusion FDRK est une des premieres cohortes nationales de patients atteints d’un cancer colorectal. Elle permettra de mieux connaitre la prise en charge de ces patients traites dans tous les types d’etablissements francais. Remerciements, financements, autres L’etude FDRK, financee par le laboratoire Roche, est pilotee par un comite scientifique independant.

In this paper, we review the consecutive methodological steps to follow when assessing clusters of adverse pregnancy outcomes (APO) in the workplace and the decisions to be taken at each step. The example of clusters of APO reported in VDT users in 1979 to 1982 is taken to illustrate each point. It appears that the number of "expected-unexpected" clusters of APO in VDT users has been largely overestimated as compared to observations and that this might be due to inadequate choices in the models used.

We reviewed the toxicologic, clinical, and epidemiologic evidence on the health effects of environmental tobacco smoke (ETS). For each type of exposure to environmental tobacco smoke we have sought articles in the English language reporting studies of effects on human health. Formal criteria that stressed study design, quality of execution and generalizability of results were used to select 116 scientifically admissible reports from over 2,900 articles. We concluded that: (a) there is strong evidence of an association between residential exposure to environmental tobacco smoke and both respiratory illness and reduction of lung function, and also between maternal smoking and reduced birth weight; (b) the weight of evidence is compatible with an association between active maternal smoking during pregnancy and increased infant mortality, and also between residential exposure to environmental tobacco smoke (primarily spousal smoking) and the risk of lung cancer; (c) there is evidence consistent with a relationship between exposure to environmental tobacco smoke in the workplace and respiratory symptoms, (d) the evidence is insufficient to implicate residential exposure to environmental tobacco smoke in relation to other forms of malignant disease or congenital malformations; (e) there is no evidence in the literature of an association between nonresidential exposure to environmental tobacco smoke and any form of cancer. Further studies are required to address the effects of exposure to environmental tobacco smoke, especially nonresidential exposure, in carcinogenesis and as a risk factor for atherosclerosis. Further work is also needed to improve measurement of exposure in such studies and to assess the importance of confounding factors.

Various high-to-low dose extrapolation models (Probit, Logit, Extreme-Value, One-Hit, Multistage) are applied to all 6 available data sets (Kociba et al. study, 1978: male and female Sprague-Dawley rats; National Toxicology Program study, 1982: male and female Osborne-Mendel rats, male and female B6C3F1 mice), in order to assess 2,3,7,8 TCDD-related carcinogenic risk at low doses. Our results show that risk assessment at low doses, based on experimental data, is limited by a huge amount of uncertainty (106 at least), according to both models and species under consideration.

INSERM established a working group to evaluate the effects of VDT work on pregnancy outcome. The group examined all available scientific papers concerning radiation emitted by VDTs, animal experimentation, and epidemiological studies. An estimation of risk was made for each outcome (congenital malformations, spontaneous abortion, stillbirth, premature birth, and low birthweight) according to a decisional algorithm, a method that gives preponderance to epidemiological arguments. On this basis, the group was able to show that the use of VDTs poses no increased risk of congenital anomalies, stillbirth, or premature birth. Consensus evaluation of divergent epidemiological results concluded that VDT work is not a risk factor significantly affecting spontaneous abortions. The risk of low birthweight could not be validly assessed.

We are presenting here an integrated decision-making algorithm for preventive action and research in public health (DAP). We reformulated several of the main stages of the elaboration of a community health programme as sets of questions or decisional nodi which lead to a decisional algorithm. The eight main stages of the DAP are the following: (1) detecting a problem, (2) is the significance of the problem well known?, (3) is our understanding of the problem sufficient for action to be initiated?, (4) defining operational objectives, (5) do we have an action strategy?, (6) are effective means available?, (7) action, (8) evaluation. We have found a place for research in six of the eight stages of the process: stages 1, 2, 3, 5, 6, 8. Some operational consequences of this categorisation and the place of research at each stage are discussed. We conclude that decision-making as to the relevance of research, must be subject to some degree of social input.

We present here and criticize the "Proposals for a Prevention Policy" drawn up by a multidisciplinary commission in France during 1982. The Report provides original elements at three conceptual levels: (i) a socio-economic model of causality of disease with a temporal, a probabilistic and a polyfactorial dimension; (ii) a social point of view brought to the concepts of health, prevention and health promotion; (iii) general principles for preventive intervention at a population level, including a breaking with the "victim-blaming" ideology. In this Report, work is always at the very center of the analysis developed by the commission. Practically, proposals are concerning work and environment on the one hand and structures and functional of public health services on the other hand. They may appear somewhat unrealistic or not clearly detailed. But one should understand that the commission essentially proposes an attitude of active involvement on the part of social actors rather than a list of concrete proposals. Undoubtedly, this French Report poses and discusses questions which are of interest even outside of the French context.

The phenolsulfotransferase (PST) is the main sulfoconjugating enzyme of catecholamines. We have described a standardized, sensitive, and reproducible method of measurement of PST activity from human blood platelets. The affinity of PST was, in descending order, towards dopamine (DA) > norepinephrine (NE) > epinephrine (E) (Km (DA) = 17.6 μM, Km (NE) = 66.6 μM, Km (E) = 330 μM). The optimum pH was found to be 5.9.Platelet PST measurements in 26 subjects led to the following observations. (i) The individual PST activity remains relatively stable during manipulations such as direct venous puncture, upright posture, physical exercise, and consumption of a copious meal. (ii) The mean platelet PST activity was 67 ± 34 (mean ± SD) U/mg protein in men and 43 ± 19 U/mg protein in women. (iii) The platelet PST activity varies during the menstrual cycle with a marked decrease 7–10 days before menstruation. (iv) Essential hypertensive patients, appearing clinically as a syndrome imitating pheochromocytoma, had absent or low conjugated catecholamines. In one of them, no PST activity could be detected in platelets using catecholamines as substrates whereas a considerable activity was present with P-nitrophenol.The potential usefulness of the platelet PST measurements is discussed.

The objectives of the study were to estimate the rate of 1-year incidence of occupational back pain, describe the duration of absence from work, and assess medical and economic aspects of this problem. A total of 2,523 files of occupational back pain, representative of the Province of Quebec for the year 1981, were examined by a multidisciplinary team. Census data from 1981 were used for the denominators. The overall 1-year incidence in 1981 was 1.37%. The age-specific incidence rates show an increase-decrease pattern that could be interpreted as a "healthy worker effect". The male to female relative risks by age range from 5.6 (20 to 24 years old) to 1.8 (55 to 64 years old). In the 1-year follow-up, 74% of the workers were absent for less than 1 month. The 7.4% of cases who were absent from work for more than 6 months accounted for nearly 75% of lost days, medical costs, and indemnity payments. We pinpoint some methodologic issues of studies on occupational back pain.

Objectives: To determine whether there is an excess of respiratory tract infections in the 5-week, 3-month, and 12-month periods before MS symptom onset and if there is an association between MS and a history of infectious mononucleosis (IM).Background: The etiology of MS remains unknown, but infection is frequently suggested as a putative etiologic agent. Epidemiologic studies have produced inconsistent evidence for an etiologic role of respiratory tract infections (RTI) and IM in MS.Methods: The authors performed a case-control study using the General Practice Research Database from the United Kingdom. There were 225 subjects with definite or probable MS, and 900 controls matched for age, sex, and physician practice. Using computerized patient records, the authors compared the mean rates of RTI per patient in the 5-week, 3-month, and 12-month periods before the date of onset of the first symptoms compatible with MS (index date). They also compared histories of IM.Results: In all periods, an increased frequency of RTI was associated with a significantly increased risk of MS. A history of IM was associated with greater than five times the risk of MS (OR = 5.5 [95% CI 1.5 to 19.7]).Conclusions: These results support an association between a history of IM and subsequent MS. Respiratory tract infections may precipitate disease onset.