Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study.

BACKGROUND: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. METHODS: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. RESULTS: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. CONCLUSIONS: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.

Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010.

The objective of this study was to evaluate the inhibitor development (ID) in previously untreated patients (PUPs) with severe haemophilia A (FVIII ≤ 0.01 IU mL(-1) ). All Canadian Haemophilia Treatment Centres completed a questionnaire on patients born between September 2005 and August 2010 and followed for up to 7 years. Eligible patients had at least 20 exposure days (ED) or had developed an inhibitor. The odds ratio (OR) and 95% confidence intervals (95% CI) for risk factors to develop an inhibitor were estimated using unconditional logistic regression. A total of 99 haemophilia A PUPs were studied. Thirty-four (34%) developed an inhibitor (24/34 of high titre). Inhibitors developed in 25/63 (40%) patients with a high-risk mutation. ID was most frequent in Aboriginals (86%). Dose intensity (IU kg(-1)  day(-1) X number of ED) at first exposure to factor VIII (FVIII) was associated with a crude OR increase of 1.10 (95% CI: 0.99-1.23) with each increase of 100 dose-intensity units. Haemarthrosis and intracranial bleeding as the indication for first exposure to FVIII concentrate were associated with a crude OR for ID of 7.63 (95% CI: 2.14-27.17) and 5.08 (95% CI: 1.11-23.31) respectively. ID according to FVIII concentrate used was: Advate (®) 18/50 (36%), Kogenate FS(®) or Helixate FS(®) 15/36 (42%), Wilate(®) 0/11 and Xyntha(®) 1/2. In multivariate analysis, Aboriginal ethnicity (OR = 11.69; 95% CI: 1.11-122.86) and haemarthrosis (OR = 4.49; 95% CI: 1.08-18.61) were statistically significant. The cumulative incidence of ID in severe haemophilia A PUPs was 34% and varied according to ethnicity, type of bleeding at first ED, type of FVIII product and dose intensity at first exposure.

A retrospective cohort study of cancer incidence among patients treated with radiosynoviorthesis.

Radiosynoviorthesis (RS) is an intra-articular injection of a radioactive colloid for the treatment of synovitis administered most often to patients with rheumatoid arthritis or haemophilia. Although highly cost-effective in comparison with surgical or arthroscopic synovectomy, the risk of cancer associated with this treatment is not well known. We evaluated the incidence of cancer in a group of patients treated with RS. A cohort of 2412 adult patients with a variety of underlying conditions (mainly rheumatoid arthritis) and treated with at least one RS between January 1976 and December 2001, was recruited from two centres in Montréal. Cancer incidence and mortality data for cohort members over that time period were obtained from regulatory agencies using linkage. Background rates for all and specific types of cancer were obtained for the provincial (Québec) and national (Canada) population according to age, gender and calendar period categories. Category-specific rates in the cohort were compared with rates in similar categories from the general population generating standardized incidence ratios (SIR). The effects of specific isotope doses and of number of RS treatments were analysed using a Cox-regression model. No increase in the risk of cancer was observed (SIR 0.96; 95% confidence interval 0.82-1.12). There was no dose-response relationship with the amount of radioisotope administered or number of RS treatments. The study provides some indication for the safety of the procedure but homogenous diagnostic groups of younger patients (such as haemophilic patients) receiving RS will need more evaluation.

Peanut allergy: is maternal transmission of antigens during pregnancy and breastfeeding a risk factor?

BACKGROUND: Peanut allergy is an important public health problem in western countries. However, the risk factors associated with this allergy remain uncertain. OBJECTIVE: To determine whether the consumption of peanuts during pregnancy and breastfeeding is a risk factor for peanut allergy in infants. METHODS: We enrolled 403 infants in a case-control study. The cases were infants aged 18 months or less with a diagnosis of peanut allergy based on a history of clinical reaction after exposure to peanuts and the presence of peanut-specific immunoglobulin E. Controls were age-matched infants with no known clinical history or signs of atopic disease. The mothers of the children filled out a detailed questionnaire about maternal diet during pregnancy and breastfeeding, the infant's diet, the presence of peanut products in the infant's environment, and family history of atopy. RESULTS: The mean (SD) age of cases was 1.23 (0.03) years. The groups were comparable in terms of the rate and duration of breastfeeding. However, the reported consumption of peanuts during pregnancy and breastfeeding was higher in the case group and associated with an increased risk of peanut allergy in offspring (odds ratio [OR], 4.22 [95% confidence interval [CI], 1.57-11.30 and OR, 2.28 [95% CI, 1.31-3.97] for pregnancy and breastfeeding, respectively). Overall, the infants with peanut allergy did not seem to be more exposed to peanut products in their environment than the controls. CONCLUSION: Early exposure to peanut allergens, whether in utero or through human breast milk, seems to increase the risk of developing peanut allergy.

Is metal fume fever a determinant of welding related respiratory symptoms and/or increased bronchial responsiveness? A longitudinal study.

BACKGROUND: The current prospective study investigated the hypothesis of metal fume fever (MFF) being a predictor for the development of respiratory symptoms and functional abnormalities. METHODS: The study consisted of a pre-exposure and two follow up assessments of 286 welding apprentices during an average period of 15 months. A respiratory and a systemic symptom questionnaire, skin prick tests to common allergens and metal salts, spirometry, and methacholine challenge tests were administered. RESULTS: Developing at least one positive skin prick test to a metallic salt solution was found in 11.8% of apprentices. Possible MFF (at least one of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, or shortness of breath) was reported by 39.2% of apprentices. The presence of at least one welding related respiratory symptom (cough, wheezing, or chest tightness) suggestive of welding related asthma was reported by 13.8%. MFF was significantly associated with these respiratory symptoms (OR = 4.92, 95% CI 2.10 to 11.52), after adjusting for age, atopy, smoking, physician diagnosed asthma, and symptoms of non-welding related asthma. Apprentices with possible MFF, and no welding related respiratory symptoms suggestive of welding related asthma at the first follow up, had an increased risk of developing the latter symptoms by the second follow up visit (OR = 7.4, 95% CI 1.97 to 27.45) compared with those not having MFF. MFF was not significantly associated with an increase in bronchial responsiveness. CONCLUSION: MFF could be a predictor for the development of respiratory symptoms but not for functional abnormalities in welders.

Myasthenia gravis after general anesthesia and hepatitis B vaccine.

A 48-year-old man presented with the first symptoms of myasthenia gravis one month after a general anesthesia and a second dose of hepatitis B plasma vaccine. Whether either event may have acted as a nonspecific challenge to the patient's immune system is speculative, but the case is described to discover similar observations, if any.

Extrahepatic uptake of technetium-99m-phytate: a prognostic index in patients with cirrhosis.

We examined the usefulness of technetium-99m-phytate (99mTc-phytate) hepatic scintigraphy in the evaluation of hepatic function, and the assessment of prognosis in patients with cirrhosis. Ninety-four patients with biopsy-documented cirrhosis had, at the time of entry into the study, a scintigraphy with 99mTc-phytate complexed with calcium in vivo. Extrahepatic uptake (EHU) of 99mTc-phytate on scintigraphy was graded from 0 (absent EHU) to 5 (important EHU) according to the relative distribution of the radiotracer between the liver, the spleen and the bone marrow. The severity of liver disease was also assessed according to the index of Child and Turcotte as modified by Pugh et al. Mean follow-up was 2 yr. EHU was correlated to the Pugh score (r = 0.73) and to survival. Survival at 2 yr was 97% for an EHU equal or inferior to 2.5, 62% for grades 3-4.5, and 31% for grade 5. In conclusion, hepatic imaging with 99mTc-phytate, in addition to its diagnostic value, also contains valuable prognostic information in patients with cirrhosis.

Relative sensitivity of different tests in the detection of low titer lupus anticoagulants.

Lupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.

Risk of childhood leukemia associated with diagnostic irradiation and polymorphisms in DNA repair genes.

The purpose of the study was to measure risk of childhood acute lymphoblastic leukemia associated with reported postnatal diagnostic X rays and to determine if it was modified in the presence of variants in genes involved in DNA repair. We conducted a population-based case-control study with 491 cases and 491 healthy controls among children 0-9 years of age at diagnosis. To evaluate gene-environment interaction, we used a subgroup of 129 cases. The adjusted odds ratio (OR) for one reported postnatal child X ray versus none was 1.04 [95% confidence interval (CI), 0.72-1.49], whereas the OR for two or more X rays was 1.61 (CI, 1.13-2.28). Among girls, the former ORs were 1.14 (CI, 0.66-1.96) and 2.26 (1. 20-4.23), respectively. Among girls who carried the hMSH3 [exon (ex) 23] variant, the ORs were 3.33 (CI, 0.75-14.82) for one X ray and 0. 27 (CI, 0.05-1.57) for two or more X rays, whereas among those who carried the XRCCI (ex 6) variant, the ORs were 1.45 (0.11-19.08) and 6.66 (0.78-56.63), respectively. On the other hand, at low levels of exposure, boys seemed protected by the variant hMLH1 (ex 8). The latter results must be interpreted with caution but suggest that the effect of diagnostic X rays could be modified by variants in repair genes according to sex. Few studies have evaluated the risk of postnatal diagnostic irradiation, which was moderately strong here; we are not aware of any studies that also considered the effect of polymorphisms in DNA repair genes. Based on the present results, both aspects deserve further study.

A framework for evaluating and conducting prognostic studies: an application to cirrhosis of the liver.

A framework for evaluating and conducting prognostic studies is proposed. Recently published studies on prognosis of cirrhosis of the liver are evaluated according to the proposed framework. It was found that appropriate statistical techniques were often used to analyze the results of prognostic studies of cirrhosis of the liver. On the other hand, the studies performed poorly with regards to study design, the determination of the usefulness of the data, the validity of the collected information, and the analytic strategy. It is hoped that the criteria suggested in this paper will improve the planning and the reporting of prognostic studies.

The psychological and physical health of family members caring for an elderly person with dementia.

Most elderly persons with dementia are cared for at home, usually by the spouse or an adult child. The objective of the present study was to determine whether there is an excess of psychological and physical health problems among family caregivers (CGs) of elderly persons with dementia. Data were obtained by interview from close family members of dementia patients (CGs), and from a comparison group made up of close family members of patients undergoing cataract surgery (non-caregivers, NCGs). CGs had significantly higher levels of depression and physical symptoms than NCGs. The association between caregiving and the health variables was stronger among subjects who were the patient's spouse than among those who were the patient's child. Furthermore, greater behavioral disturbance in the demented patient was associated with higher levels of morbidity in the CG. The results suggest that CGs might benefit from careful monitoring of their health status, and from greater access to specialized support services.

Use of physician services among family caregivers of elderly persons with dementia.

It is well known that there is an excess of physical and psychological health problems among family caregivers of elderly persons with Alzheimer's disease and other dementias. The objective of this study was to determine whether the higher level of morbidity translates into a higher level of medical care utilization. Data from a previously completed longitudinal study of caregivers for elderly persons with dementia were merged with data on physician visits obtained from the computerized records of the Quebec Health Insurance Board. Utilization of physician care (adjusted for age, sex, number of chronic diseases, and depression) was no higher for family caregivers of elderly patients with Alzheimer's disease and other dementias than for comparable family members of older persons without dementia. The annual cost of physician care was almost identical among caregivers and noncaregivers. However, the pattern of utilization for the two groups was somewhat different: there was a significantly higher frequency of physician utilization among caregivers for services billed by psychiatrists and internal medicine specialists. In multivariate analysis, physician utilization was significantly associated with having more than one chronic condition and with increased age. Future studies should focus on determining whether caregivers neglect their own health care needs as a result of the exigencies of the caregiving role.

Airway hyperresponsiveness and symptoms of asthma in a six-year follow-up study of childhood asthma.

BACKGROUND AND AIM: In an inception cohort study of 457 asthmatic children diagnosed at the age of 3 to 4 years, airway hyperresponsiveness (AHR) was assessed 6 years after first diagnosis in a subgroup of 84 children. Our objective was to associate the level of AHR with the symptomatic asthma status at follow-up. METHODS: Information on respiratory symptoms and medication use for the previous 6 years was obtained. Children with reported wheezing episodes during the previous year (n = 169) or for > or = 2 years at any time during the follow-up period (n = 85) were eligible for the challenge test. RESULTS: Among the 254 eligible children, 166 were randomly selected. The parents of 88 of them consented to have their child participate. At the time of assessment of AHR, 19 children (22%) were asymptomatic and 24 others (29%) had symptoms but did not use any medication. Forty-one children (49%) were symptomatic and required medication, including antiinflammatory preparations in 26 instances (31%). All but two children had significant AHR. There was no significant association between the level of AHR and graded symptomatic and medication score. Twenty-four of the 70 children (34%) with greatly enhanced AHR used no medication. CONCLUSIONS: This study shows that (1) almost all children first diagnosed with asthma 6 years ago and with persisting but not necessarily current symptoms of asthma have increased AHR, which satisfies a proposed epidemiologic definition of asthma; (2) AHR was present in 95% of the 20 currently asymptomatic children; and (3) one third of children with greatly enhanced AHR did not use any treatment.

Congenital anomalies in children with acute lymphoblastic leukaemia and in their family.

BACKGROUND: With the exception of Down syndrome the association between congenital anomalies and acute lymphoblastic leukaemia (ALL) is presently unclear. We investigated this association in a population-based case-control study carried out in the province of Québec, CANADA: METHODS: A total of 491 incident cases diagnosed between 1980 and 1993 and aged 0-9 years were included in the study. Healthy controls (n = 491) matched on age, sex, and region of residence at the time of diagnosis were selected from government family allowance files. Using a structured questionnaire and the International Classification of Diseases (Ninth Revision) list of congenital anomalies, presence of an anomaly was determined by interviewing the parents of the study subjects; mothers gave information on anomalies in the study subject, their siblings and her family, whereas fathers provided information on anomalies in their family. RESULTS: The adjusted risk for ALL was not increased in children who had any anomaly (odds ratio [OR] = 1.07 [95% CI : 0.70-1.65]) whereas compared to control siblings, case siblings had a higher risk of anomalies (OR = 1.54, 95% CI : 0.99- 2.42). This increase was likely due to excesses in anomalies of the heart (OR = 2.49, 95% CI : 1.23-5.04). Risk for ALL was elevated in children with a history of a congenital anomaly in their mother (OR = 1.61, 95% CI : 0.80-3.22) or her family (OR = 1.45, 95% CI : 0.94-2.25). CONCLUSIONS: Although based on small numbers for specific anomalies, these findings suggest that congenital anomalies are more prevalent in siblings and maternal family of ALL cases than in controls.

A telephone support service to reduce medical care use among the elderly.

A randomized controlled trial was performed to determine whether a telephone support system could reduce the frequency of ambulatory physician encounters. A total of 182 elderly persons were enrolled in the study. The experimental group was regularly called by a public health nurse and could call the nurse every weekday during normal working hours. The control group received no intervention. A year later, the experimental group reported 7.40 ambulatory encounters with a physician (SD = 4.94) and the control group reported 8.61 encounters (SD = 6.85). The difference between the groups, after adjusting for various prognostic factors, was 1.20 (95% confidence interval, -0.84 to 3.24). Although the difference did not achieve statistical significance, the results suggest that telephone support may bring about a substantial decrease in medical care utilization. Further research assessing the cost-advantage ratio for this type of intervention is recommended.

Folate deficiency among institutionalized elderly. Public health impact.

All patients 65 years and older who had been living in an institution for at least six months had a measurement of red blood cell folate (RBCF), serum folate (SF), vitamin B12, hemoglobin, and mean corpuscular volume. Twenty-two percent of the 97 studied subjects were found deficient in RBCF, although only 6% had anemia. Length of stay at the institution was significantly associated with deficiency in RBCF and this association was uncon-founded by age. The proportion of RBCF deficiency among the studied subjects attributable to length of stay is 80%. The prophylactic administration of folate among long-term nursing home type of patients should be considered.

Acute lymphoblastic leukaemia among Spanish children and mothers' occupation: a case-control study.

STUDY OBJECTIVE: The aim was to investigate the association between mothers' occupational exposure during pregnancy and the incidence of acute lymphoblastic leukaemia in children. DESIGN: The study was a case-control investigation. A face to face interview was used to assess exposures at work and relevant confounding variables. SETTING: The study was community based and was carried out in five provinces of Spain. SUBJECTS: 128 cases less than 15 years of age were interviewed (91% of those eligible). Controls (one for each case) were chosen from the census lists and were matched on year of birth, sex and municipality. MEASUREMENTS AND MAIN RESULTS: Children of mothers working at home had a relative risk (RR) of 7.0 (95% CI = 1.59-30.79) of developing acute lymphoblastic leukaemia. Exposure to organic dust was associated with a RR of 5.5 (95% CI = 1.21-24.8). There was a statistically significant interaction between exposure to organic dust and working at home. The majority of women working at home were hired by local industries to sew different types of tissues (cotton, wool, synthetic fibres) on a machine. CONCLUSION: A similar association has not been reported before: if confirmed, this finding may suggest a new health concern.

Evaluation of a mutual help network for the elderly residents of planned housing.

We set up a mutual help network among the elderly residents of a government-subsidized apartment building and evaluated its impact on their social ties, social support satisfaction, and depression. A quasi-experimental design was used, with the residents of a similar building located in the same neighborhood serving as the control group. A total of 230 individual services were exchanged, and 28 group activities were organized during the study period. There was almost no difference between experimental and control groups with respect to the change over the study period in the number of social ties with other residents of the building. Support satisfaction decreased in both groups, but the decrease was larger in the experimental group. The control group had a slight decrease in the frequency of their depressive symptoms, whereas the experimental group had a moderate increase. More research is needed on the ability of social support interventions to produce beneficial effects on mental health among individuals who are not experiencing a particular life stress.

Circadian time-dependent response of childhood lymphoblastic leukemia to chemotherapy: a long-term follow-up study of survival.

The evolution of 118 children treated for acute lymphoblastic leukemia between 1976 and 1984, and followed until 1991, was reviewed. Maintenance chemotherapy consisted of daily 6-mercaptopurine (6-MP), weekly methotrexate (MTX), and monthly vincristine and prednisone. Eighty-two children took 6-MP and MTX in the morning, and 36 took them in the evening. Disease-free survival, as determined by Kaplan-Meier analysis, was better for children on evening chemotherapy. Regression analysis (Cox proportional hazards model, with evening versus morning schedule as exposure variable, and age at diagnosis, leucocytosis at diagnosis, and sex as covariates) showed that for those surviving free of disease for longer than 78 weeks, the risk of relapse was 2.56 times greater for the morning schedule than for the evening one.

Low birth weight and household structure.

Data collected during postnatal visits were used to study the risk of low birth weight (LBW) among unmarried women living alone and among unmarried women living with a partner or another adult, using married women living with their husbands as the reference group. Information on 1,627 singleton live births was included in a binomial regression, controlling for seven potential confounding variables: mother's age, education, gestational weight gain, parity, smoking status, and presence of medical problems preceding or during pregnancy. Unmarried women living alone were at greater risk of bearing a LBW infant than married women living with their husbands (RR = 2.0, 95% Cl = 1.2-3.4). Unmarried women living with a partner had a slightly lower risk of LBW than married women (RR = 0.6, 95% Cl = 0.3-1.3) and unmarried women living with another adult had a slightly increased risk (RR = 1.3, 95% Cl = 0.6-3.0), although neither of these results was statistically significant. On the basis of these findings, we suggest that public health interventions should target women according to their household structure rather than their marital status.