Impact of Chronic Levels of Naturally Multi-Contaminated Feed with Fusarium Mycotoxins on Broiler Chickens and Evaluation of the Mitigation Properties of Different Titers of Yeast Cell Wall Extract.

The chronic intake of naturally multi-mycotoxin contaminated feed by broilers with or without titers of Yeast Cell Wall Extract (YCWE, a.k.a Mycosorb A+®), was investigated. Day-old male Cobb chicks (1600 birds, 64 pens, 25 birds/pen) were randomly allocated to diets of control (CON); diet containing mycotoxins (MT); CON + 0.2% YCWE; MT + 0.025% YCWE; MT + 0.05% YCWE; MT + 0.1% YCWE; MT + 0.2% YCWE; and MT + 0.4% YCWE. Growth performance, blood biochemical parameters and gut health were recorded over 42 days. Compared with CON, MT had reduced body weight (BW) and increased feed conversion ratio (FCR) on days 35 and 42 with increased duodenal crypt depth and fewer goblet cells. Furthermore, European Poultry Production Efficiency (EPEF) was reduced for MT versus CON. Feeding MT + 0.2% YCWE improved BW, lowered FCR, reduced crypt depth, increased goblet cell count and improved EPEF. Considering titration of YCWE (0 to 0.4%) during mycotoxin challenge, a cubic effect was observed for FCR with NC + 0.2% YCWE having the lowest FCR. These findings suggest that chronic consumption of multiple Fusarium mycotoxins present in common field concentrations can negatively impact broiler performance and gut health while inclusion of YCWE, particularly 0.2%, could be effective in counteracting mycotoxins.

Effects of a mannan-rich yeast cell wall-derived preparation on cecal concentrations and tissue prevalence of Salmonella Enteritidis in layer chickens.

Salmonella Enteritidis (SE) has been the most common Salmonella serotype associated with foodborne infections in the last several years. Dietary applications of yeast-based preparations in feed have shown to reduce Salmonella colonization in chickens augmenting SE control strategies. This study was conducted to evaluate the effects of a mannan-rich yeast cell wall-derived preparation (Actigen®) administered in feed at a rate of 400 g/ton on SE colonization in the cecum and internal organs of commercial layer chickens. Sixteen week-old layer pullets were orally challenged with a selected nalidixic acid resistant SE strain at a dose of 1.7×10^9 colony forming units (CFU) per bird. SE colonization was assessed by evaluating isolation rates from ovary and pooled liver/spleen samples as well as enumeration of SE in cecal pouches one week post-challenge. Recovery rates of SE from the ovaries of directly challenged birds receiving Actigen® were significantly lower (P <0.02) than those in directly challenged birds fed an unsupplemented control diet. Recovery rates of SE from pooled liver/spleen samples were not significantly different between Actigen®-treated pullets and controls (P = 0.22). Using direct plate count methods, cecal SE concentrations were 1 log10 lower (P <0.001) in challenged pullets in the Actigen®-supplemented group than in the challenged controls. The SE concentration distributions in the ceca were similar in groups testing positive and groups testing negative for SE in the ovaries and liver/spleens tissues. As a result, SE concentrations in the ceca could not be directly related to the occurrence or prevalence of SE in these tissues. In conclusion, Actigen® supplementation appears to decrease the prevalence of SE in ovarian tissue and concentrations of SE in cecal contents and may be useful as a tool for reducing the risk of eggshell contamination and transovarian transmission of SE in eggs.

Can dietary zinc diminish the impact of necrotic enteritis on growth performance of broiler chickens by modulating the intestinal immune-system and microbiota?

The objective of this study was to compare the effects of inorganic and proteinate Zn in chickens challenged with coccidia and Clostridium perfringens. A 3 × 2 factorial design was used, with 3 dietary formulations (0 or 90 mg/kg supplemental Zn from ZnSO4 or Zn proteinate, with or without challenge). On day 14, challenged birds were orally gavaged with approx. 5,000 Eimeria maxima sporulated oocysts, and on day 19 to 21 with C. perfringens (108 CFU/D). Productive performance was assessed at day 21 and 28. At 21 D, necrotic enteritis (NE) lesion severity, intestinal permeability, gene expression, and ileal and cecal microbiota were evaluated. An interaction of Zn source by challenge was observed for lesion score and mortality, wherein Zn supplementation decreased the degree of NE lesions (P = 0.02) and mortality due to NE (P = 0.008). In the jejunum, an interaction of Zn source by challenge was observed for the expression of IL-8 (P = 0.001) and INF-γ (P = 0.03), wherein the NE challenge upregulated their expression, but not in the Zn proteinate supplemented birds. Zn proteinate supplementation downregulated iNOS vs. ZnSO4 supplemented birds (P = 0.0003), and supplemental Zn downregulated TLR-2 (P = 0.05) and ZnT5 (P = 0.04), regardless of the source. In the ileal microbiota, Zn proteinate supplementation decreased the frequency of Lactobacillus (P = 0.01), and the challenge increased Enterobacteriaceae (P = 0.01). Dietary Zn decreased NE lesion severity and mortality due to NE; Zn proteinate led to lower expression of IL-8 and INF-γ in challenged birds which may be an indicative of a lessened inflammatory response.

Zinc source modulates intestinal inflammation and intestinal integrity of broiler chickens challenged with coccidia and Clostridium perfringens.

Two dietary sources of zinc (ZnSO4 or organic Zn) were tested in chickens challenged with coccidiosis (Co) or coccidiosis plus Clostridium perfringens (CoCPF). On day 14, the chickens were orally gavaged with ∼5,000 Eimeria maxima sporulated oocysts. On day 19, 20, and 21 chickens challenged with C. perfringens were given a broth culture containing 108 cfu of this bacterium. Productive performance parameters were determined at d 14, 21, and 28. On day 21, necrotic enteritis (NE) lesions were scored, and intestinal permeability was evaluated. Jejunum and cecal tonsils were collected for morphology and gene expression analysis. On day 21, organic Zn improved BW gain by 18.6% (P = 0.07), and FCR by 12% (P = 0.09) in CoCPF challenged chickens vs. birds fed ZnSO4. From 1 to 28, organic Zn increased BW gain (P = 0.02), and improved FCR (P = 0.03) vs. birds fed ZnSO4. At 21 d, NE lesions were only observed in CoCPF birds (P < 0.001), and mortality due to NE was only observed when CoCPF birds were fed ZnSO4 (P = 0.001). Organic Zn fed birds had increased villus height in the jejunum (P = 0.005) and decreased intestinal permeability (P = 0.01) vs. ZnSO4. In the jejunum, organic Zn fed birds showed a downregulation of expression of IL-8 (P = 0.02), and upregulation of IL-10 (P = 0.05) in CoCPF birds vs. ZnSO4- CoCPF birds. As main effect, birds supplemented with organic Zn had higher mRNA expression of TLR-2 (P = 0.02) and IgA (P = 0.01). In the cecal tonsils, organic Zn fed birds showed upregulation of iNOS (P = 0.008) in CoCPF birds vs. ZnSO4-CoCPF birds. Organic Zn supplementation reduced intestinal permeability and attenuated intestinal inflammation of broilers co-challenged with coccidia and C. perfringens.

Zinc source influences the gene expression of zinc transporters in jejunum and cecal tonsils during broiler challenge with Eimeria maxima and Clostridium perfringens.

The objective of this experiment was to study the effects of dietary zinc (Zn) source on gene expression of Zn transporters (metallothionein [MT], ZIP 3, 5, 8, 9, 10, 11, 13, and 14, and ZnT 1, 4, 5, 6, 7, 9, and 10) in the jejunum and cecal tonsils of broilers challenged with coccidia or coccidia plus Clostridium perfringens. A 2 × 2 factorial design was used with 2 Zn sources (90 mg Zn/kg from either ZnSO4 or an organic Zn, Bioplex® Zn) and challenged with approximately 5,000 oocysts of Eimeria maxima at 14 d of age with or without C. perfringens (108 CFU/bird) at 18, 19, and 20 d of age (8 pens per treatment and 8 birds per pen) after which 1 bird/pen was sampled at 21 d of age. In the jejunum, co-infection resulted in higher ZnT 5 and 6 gene expression, while organic Zn fed birds had lower ZIP 5 and 11, and higher ZnT1. Additionally, an interaction of challenge by Zn source was noted wherein ZnT10 was unaffected by the C. perfringens in the organic Zn treatment but was 2.7-fold lower in the co-infected ZnSO4 fed birds. S100A9 gene expression, a biomarker of inflammatory response in necrotic enteritis, increased 2 and 2.8-fold in the cecal tonsils and jejunum with the co-infection, respectively. Supplementation with organic Zn lowered S100A9 by 1.9 and 4.4-fold in the cecal tonsils and jejunum, respectively, when birds were supplemented with ZnSO4. Notably, MT, ZIP 3, 8, 9, 10, 13, or 14, and ZnT 4, 7, and 9 were unaffected by Zn source and/or method of challenge. An interaction of challenge by Zn source was also noted for serum Zn concentration, which was reduced when birds were challenged with C. perfringens and fed ZnSO4 but no difference between challenge method when birds were fed organic Zn. Based on the expression of ZnT and ZIP genes, more Zn trafficking due to treatment occured in the jejunum than cecal tonsils, but further studies are needed to ascertain how Zn source regulates intracellular free Zn concentrations and whole-body Zn status during an enteric challenge.

The Effect of Waiting Times for Postoperative Radiotherapy on Outcomes for Women Receiving Partial Mastectomy for Breast Cancer: a Systematic Review and Meta-Analysis.

AIMS: To determine the effect of delay in postoperative radiotherapy on local recurrence and overall survival in women receiving partial mastectomy for breast cancer. MATERIALS AND METHODS: This was a systematic review and meta-analysis of published literature. Relevant reports were identified from MEDLINE, EMBASE and the Cochrane Register of Controlled Trials in all languages from 1975 to April 2015, in addition to the abstracts from the annual meetings of major radiotherapy conferences from 2000 to 2011. Reference lists were hand searched to find additional relevant reports and OvidSP's 'Find Citing' function was used to find studies citing papers identified in the primary search. Studies were included if they met the following criteria: (i) all patients received partial mastectomy and radiotherapy, (ii) a delay from surgery to radiotherapy was reported and (iii) one or more of local control/failure and/or survival were reported. Observational studies and randomised controlled trials were included. Studies including patients with in situ disease were excluded. Studies were classified as high quality if they adequately controlled for factors known to be associated with the outcomes of interest. Study quality was independently assessed by three authors. Initial disagreements about three studies were resolved by consensus. Only high-quality studies were included in the primary analysis. Delay was modelled as a continuous variable and the relative risk of local recurrence and the relative risk of death are reported per month of delay. The study results were combined using a fixed-effects model. RESULTS: Thirty-four relevant publications including 79 616 patients were identified in the systematic review. Ten high-quality publications reported on local recurrence (13 291 patients) and four high-quality studies reported on overall survival (2207 patients). The relative risk of local recurrence per month of delay was 1.08 (95% confidence interval 1.02-1.14). The relative risk of death per month of delay was 0.99 (95% confidence interval 0.94-1.05). CONCLUSIONS: Delays in post-lumpectomy radiotherapy are associated with a significant increase in the risk of local recurrence. We recommend that waiting times for radiotherapy should be kept as short as reasonably achievable.

Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice.

INTRODUCTION: Randomized controlled trials (rcts) are the "gold standard" for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and□ compare the effectiveness of ppdc in routine practice with its efficacy in rcts. METHODS: Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario's regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient's symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas "well-being" item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts. RESULTS: We identified 906 patients with pre-ppdcesas records. Median survival was 31 weeks compared with 28-48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%-63% who had improved or stable qol in rcts. CONCLUSIONS: The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.

Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case-control studies.

Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection practices and DBPs occurrence between both continents, specific risk estimates for bladder cancer in relation to DBPs exposure for European populations were needed. We conducted a pooled and a two-stage random-effect meta-analyses of three European case-control studies from France, Finland, and Spain (5467 individuals: 2381 cases and 3086 controls). Individual exposure to THMs was calculated combining information on residential history, estimates of the average total THMs (TTHM) level in tap water at the successive residences and personal water consumption. A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 µg/l (OR = 1.47 (1.05; 2.05)) when compared to men exposed to levels ≤ 5 µg/l. The linear trend of the exposure-risk association was significant (p = 0.01). Risks increased significantly for exposure levels above 25 µg/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion. There was no evidence of a differential exposure-response relation for TTHM and bladder cancer in Europe and North America. Consequently, a global exposure-risk relation based on 4351 cases and 7055 controls is now available.

Racial, gender and geographic disparities of antiretroviral treatment among US Medicaid enrolees in 1998.

BACKGROUND: In 1998, highly active antiretroviral therapy (HAART) was widespread, but the diffusion of these life-saving treatments was not uniform. As half of all AIDS patients in the USA have Medicaid coverage, this study of a multistate Medicaid claims dataset was undertaken to assess disparities in the rates of HAART. METHODS: Data came from 1998 Medicaid claims files from five states with varying HIV prevalence. ICD-9 codes were used to identify people with a diagnosis of HIV/AIDS or AIDS-defining illness. Multivariate analyses assessed associations between age, gender, race and state of residence for antiretroviral regimens consistent with HAART, as defined by 1998 Centers for Disease Control and Prevention (CDC) guidelines. RESULTS: Among 7202 Medicaid enrolees with a diagnosis of HIV/AIDS or AIDS, 62% received HAART and 25% received no antiretroviral therapy. Multivariate analyses showed that age, race, gender and state were all significant predictors of receiving HAART: white, non-Hispanic patients were most likely to receive HAART (68.3%), with lower rates in Hispanic and black, non-Hispanic segments of the population (59.3% and 57.5%, respectively, p<0.001). Women were less likely to receive HAART than men (51.8% vs 69.3%, p<0.001). CONCLUSION: Despite similar insurance coverage and drug benefits, life-saving treatments for HIV/AIDS diffused at widely varying rates in different segments of the Medicaid population. Research is needed to determine the extent to which racial, gender, interstate and region disparities currently correspond to barriers to such care.

Haloacetic acids in drinking water and risk for stillbirth.

BACKGROUND: Trihalomethanes (THMs) occurring in public drinking water sources have been investigated in several epidemiological studies of fetal death and results support a modest association. Other classes of disinfection by-products found in drinking water have not been investigated. AIMS: To investigate the effects of haloacetic acid (HAA) compounds in drinking water on stillbirth risk. METHODS: A population based case-control study was conducted in Nova Scotia and Eastern Ontario, Canada. Estimates of daily exposure to total and specific HAAs were based on household water samples and questionnaire information on water consumption at home and work. RESULTS: The analysis included 112 stillbirth cases and 398 live birth controls. In analysis without adjustment for total THM exposure, a relative risk greater than 2 was observed for an intermediate exposure category for total HAA and dichloroacetic acid measures. After adjustment for total THM exposure, the risk estimates for intermediate exposure categories were diminished, the relative risk associated with the highest category was in the direction of a protective effect, and all confidence intervals included the null value. CONCLUSIONS: No association was observed between HAA exposures and stillbirth risk after controlling for THM exposures.

Coffee and tea consumption and cancers of the bladder, colon and rectum.

Coffee has been observed to be associated weakly or not at all with bladder cancer risk, inversely with colon cancer risk, and inconsistently with rectal cancer risk. The association between these cancers and consumption of coffee and tea was examined in a single case-control study conducted in Ontario, Canada from 1992 to 1994. A questionnaire was filled out by 927 bladder cancer cases, 991 colon cancer cases, 875 rectal cancer cases, and 2118 population controls. Although bladder cancer risk was not associated with coffee or tea, risk estimates associated with coffee among subjects who had never smoked were non-significantly increased. Colon cancer risk was inversely associated with coffee. Relative to those drinking less than 1 cup of coffee per day, the odds ratios (OR) for those drinking 1-2 cups was 0.9 (95% CI 0.8-1.1), for those drinking 3-4 cups was 0.8 (95% CI 0.7-1.0), and for those drinking 5 or more cups was 0.7 (95% CI 0.5-0.9); these ORs decreased linearly (P = 0.008). The reduced risk estimates were more pronounced with cancer of the proximal colon than the distal colon. Rectal cancer risk was not associated with either coffee or tea. Coffee consumption was observed to have a different relationship for each of the cancer sites and tea consumption was not related to any cancer site.

An ecologic study of childhood leukemia and population mixing in Ontario, Canada.

OBJECTIVE: To examine the association between population mixing and the incidence of childhood leukemia, specifically the acute lymphocytic leukemia (ALL) subtype among young children. METHODS: This ecologic study was based on incidence rates of leukemia in children aged 0-14 years. The Ontario Cancer Registry was used to identify the residence of 1394 leukemia cases between 1978 and 1992. Ecologic units were composed of census subdivisions in a 5-year period. Percent population change, determined from the Census of Canada, was employed as a measure of population mixing. The relationship between population mixing and childhood leukemia was examined separately after stratifying by the level of geographic isolation, defined according to urban-rural status. Analyses were also conducted separately in specific age groups and for the ALL subtype. RESULTS: Population growth in rural areas was associated with an increased incidence of leukemia, particularly for the ALL subtype in children aged 0-4 years (rate ratio = 1.8, 95% confidence interval 1.1-2.8, for a greater than 20% population change relative to no increase in population). In contrast, an elevated risk due to population mixing was not observed in urban areas. CONCLUSIONS: Results from this study are consistent with results from similar studies conducted in the United Kingdom, which are suggestive of a role for an infectious agent in the etiology of childhood leukemia, as proposed in the Kinlen hypothesis.

Relation between trihalomethane compounds and birth defects.

OBJECTIVES: To evaluate the risk of birth defects relative to exposure to specific trihalomethanes in public water supplies. METHODS: A retrospective cohort study was conducted based on data from a population based perinatal database in Nova Scotia, Canada and from the results of routine water monitoring tests. The cohort consisted of women who had a singleton birth in Nova Scotia between 1988 and 1995 and who lived in an area with a municipal water supply. The birth defects analyzed included neural tube defects, cardiovascular defects, cleft defects, and chromosomal abnormalities. Two of the four trihalomethane compounds occur in large enough concentrations to be analyzed (chloroform and bromodichloromethane (BDCM)). RESULTS: Exposure to BDCM at concentrations of 20 microg/l or over was associated with an increased risk of neural tube defects (adjusted relative risk (RR) 2.5, 95% confidence interval (95% CI) 1.2 to 5.1) whereas exposure to chloroform was not. Exposure to BDCM of 20 microg/l and over was associated with decreased risks of cardiovascular anomalies (RR 0.3, 95% CI 0.2 to 0.7). There was a suggestion of an increased risk of chromosomal abnormalities associated with exposure to chloroform, and no evidence of any association between either trihalomethane compound and cleft defects. CONCLUSIONS: In this cohort, differences were found in the RR associated with exposure to chloroform and BDCM for each of the congenital anomalies under study. These findings point to the importance of examining specific byproduct compounds relative to risk for these birth outcomes and in particular implicate BDCM and other correlated disinfection byproducts in the aetiology of neural tube defects.

Measurement of pediatric illness severity using simple pretransport variables.

OBJECTIVE: To test the hypothesis that pretransport variables can predict in-hospital mortality that will correlate with major interventions and unplanned events during interfacility transport. METHODS: A cohort of children (n = 2,253) transported by a specialized pediatric team to a children's hospital were studied. At the time of referral, data collected included age (months), heart rate, systolic blood pressure, respiratory rate, retractions, stridor or wheezing, seizures, skin perfusion, oxygen requirement, and mental status. Using univariate and stepwise logistic regression, variables predictive of in-hospital mortality were selected from a training set (n = 1,111) and assigned integers based on their computed coefficients. Probability of in-hospital mortality was calculated using the total integer score and age. The risk of mortality derived from the training set was validated in the remaining patients (n = 1,142) by comparing the observed and predicted mortalities. Major interventions performed and unplanned events were determined for each of five predetermined mortality risk groups. RESULTS: Variables (integers) predicting in-hospital mortality included systolic blood pressure (11), respiratory rate (6), oxygen requirement (11), and altered mental status (11). Observed mortality was similar to predicted mortality in all risk categories for the validation sample. As risk of mortality increased, so did the performance of major interventions and the occurrence of unplanned events. CONCLUSION: Four pretransport variables predicted in-hospital mortality. Risk of mortality correlated with the incidence of major patient interventions, and the occurrence of unplanned events increased as well. This model might be useful in comparing different transport systems using severity-adjusted assessment of children requiring interfacility transport.

Relation between stillbirth and specific chlorination by-products in public water supplies.

During water treatment, chlorine reacts with naturally occurring organic matter in surface water to produce a number of by-products. Of the by-products formed, trihalomethanes (THMs) are among the highest in concentration. We conducted a retrospective cohort study to evaluate the relationship between the level of total THM and specific THMs in public water supplies and risk for stillbirth. The cohort was assembled from a population-based perinatal database in the Canadian province of Nova Scotia and consisted of almost 50,000 singleton deliveries between 1988 and 1995. Individual exposures were assigned by linking mother's residence at the time of delivery to the levels of specific THMs monitored in public water supplies. Analysis was conducted for all stillbirths and for cause-of-death categories based on the physiologic process responsible for the fetal death. Total THMs and the specific THMs were each associated with increased stillbirth risk. The strongest association was observed for bromodichloromethane exposure, where risk doubled for those exposed to a level of [greater and equal to] 20 microg/L compared to those exposed to a level < 5 microg/L (relative risk = 1. 98, 95% confidence interval, 1.23-3.49). Relative risk estimates associated with THM exposures were larger for asphyxia-related deaths than for unexplained deaths or for stillbirths overall. These findings suggest a need to consider specific chlorination by-products in relation to stillbirth risk, in particular bromodichloromethane and other by-product correlates. The finding of a stronger effect for asphyxia deaths requires confirmation and research into possible mechanisms.

Case-control study of colon and rectal cancers and chlorination by-products in treated water.

This population-based case-control study was conducted in southern Ontario, Canada from 1992 to 1994 to assess the relationship between chlorination by-products in public water supplies and cancers of the colon and rectum. Interviews providing residence and water source histories were completed by 76% of eligible cancer cases and 72% of eligible controls. Supplemental data from municipal water supplies were used to estimate individual exposure to water source, chlorination status, and by-product levels as represented by trihalomethanes (THMs) during the 40-year period before the interview. The analyses included 767 colon cases, 661 rectal cases, and 1545 controls with exposure information for at least 30 of these years (75% of subjects with completed interviews). Among males, colon cancer risk was associated with cumulative exposure to THMs, duration of exposure to chlorinated surface water, and duration of exposure to a THM level > or = 50 microg/liter and 75 microg/liter. Males exposed to chlorinated surface water for 35-40 years had an increased risk of colon cancer compared with those exposed for < 10 years (odds ratio, 1.53; 95% confidence interval, 1.13-2.09). Males exposed to an estimated THM level of 75 microg/liter for > or = 35 years had double the risk of those exposed for < 10 years (odds ratio, 2.10; 95% confidence interval, 1.21-3.66). In contrast, these relationships were not observed among females. No relationship was observed between rectal cancer risk and any of the measures of exposure to chlorination by-products. The results of this study should be interpreted with caution because they are only partially congruent with the limited amount of literature addressing this issue.

Evaluation of emergency department referrals by telephone triage.

OBJECTIVE: Telephone triage programs are becoming very common at children's hospitals across the nation. One of the proposed benefits of these programs is the more efficient use of health care resources by triaging patients to the appropriate level of health care. The purpose of this study is to examine the appropriateness of referrals to a pediatric emergency department (ED) by the Pediatric Health Information Line (PHIL), a hospital-based telephone triage program, versus all other sources of referrals. METHODS: A blinded Delphi rating system was used to review the physician's sheets of 133 consecutive ED referrals by PHIL for medical appropriateness. A total of 260 randomly selected control patients seen in the ED during the same period were similarly reviewed. If 2 of 3 pediatric emergency medicine physicians agreed that an ED visit was appropriate, then it was considered appropriate. A comparison of the 2 groups' ED appropriateness was made using a contingency table chi(2) test. An odds ratio with confidence limits was also calculated. Demographic data were collected for both groups including age, race, gender, and insurance status. RESULTS: The PHIL group had an appropriateness rate of 80.2%, compared with 60.5% for the control group (chi(2) = 14.6369; odds ratio = 2.65; 95% confidence interval [1.5759,4.5008]). CONCLUSIONS: This demonstrated that for the period studied, PHIL referrals to the ED had a 33% higher rate of appropriateness than controls. This evidence supports telephone triage as an efficient gatekeeper for health care resources.

Suicides among Canadian farm operators.

The objective of this epidemiologic study was to describe rates of suicide among male farm operators in Canada and to compare rates with those in the general male population. The data were obtained from the Canadian Farm Operator Cohort (CFOC) database. Outcome measures were age-specific and age-standardized rates of completed suicide (ICD-9-CM E-codes 950-959). A total of 1,457 cases of suicide were identified from the CFOC for the years 1971- 1987. Age-standardized rates of suicide for those aged 30-69 were 29.2 (95% CI = 27.3-31.1) per 100,000 person-years (PYs) in the CFOC, 24. 0 (95% CI = 22.1-25.8) per 100,000 PYs in the CFOC excluding Quebec (which had data linkage concerns) and 27.0 (95% CI = 26.6-27.3) per 100,000 PYs among Canadian males in general. Age-specific rates of suicide in the CFOC increased over time. After adjustment for age differences, provincial suicide rates among farm operators were generally lower than or equivalent to those observed in the comparison populations of Canadian males. The implications of these results are discussed. We speculate that high levels of social support traditionally available in Canadian farm communities may protect farm operators from abnormally high rates of suicide.

Effect of ketorolac in pediatric sickle cell vaso-occlusive pain crisis.

BACKGROUND: Ketorolac is a parenteral, nonsteroidal analgesic that does not have a narcotic's risks of respiratory depression, hypotension, or dependence. Its usefulness in providing pain relief in pediatric patients with acute vaso-occlusive crisis of sickle cell disease has not been studied to date. METHODS: Twenty-nine patients with sickle cell disease between the ages of 5 and 18 years who presented to The Children's Hospital of Alabama emergency department (ED) with 41 distinct episodes of acute vaso-occlusive pain crisis were enrolled prospectively and randomized to receive either 0.9 mg/kg intravenous (IV) ketorolac or placebo in a double-blind fashion. All patients also received IV fluids and an initial 0.1 mg/kg of IV morphine. Subsequent standardized doses of morphine were given every 2 hours over a 6-hour observation period based upon severity of pain as scored by a 10-cm linear visual analog scale (VAS). Vital signs and pain severity were recorded initially and assessed hourly. Disposition was made at the end of the observation period. RESULTS: Patients receiving ketorolac and those receiving placebo were of similar age, weight, gender, number of prior ED visits, number of prior hospital admissions, duration of pain prior to presentation, and initial pain score. The total dose of morphine received, reduction in severity of pain as measured by VAS, rate of hospital admission, and rate of return to the ED for discharged patients did not differ significantly between the two groups. CONCLUSION: We were unable to demonstrate a synergistic analgesic effect for ketorolac in the treatment of pain from acute vaso-occlusive crisis in pediatric sickle cell disease. Further investigations involving larger samples of sickle cell patients may be needed to further define a role for ketorolac in the acute management of sickle cell vaso-occlusive pain.

Association of cutaneous malignant melanoma with intermittent exposure to ultraviolet radiation: results of a case-control study in Ontario, Canada.

BACKGROUND: Although solar radiation is well established as a risk factor for melanoma, it is less clear how the pattern and timing of exposure to ultraviolet (UV) radiation might be important. The particular objective of this study was to evaluate the association of melanoma risk with various measures of intermittent and chronic exposures to UV radiation, and to assess how these exposures interact with other risk factors such as skin type. METHODS: Data were analysed from a large case-control study (583 cases, 608 controls) of malignant melanoma, carried out in southern Ontario, Canada. RESULTS: Significant risk increases were identified with several measures of intermittent exposure, including beach vacations in adolescence and in the past 5 years, previous sunburn, and use of sunbeds and sunlamps. Chronic exposure, indicated by days of outdoor activity during adolescence and by occupation in recent adult life, was associated with significantly reduced risk. Subgroup analyses showed: no major risk differences by body site of melanoma; stronger association of lentigo maligna melanoma with intermittent exposure; more pronounced effects of beach vacations and sunburn in younger subjects; and consistently higher risks for intermittent exposures among subjects with skin more susceptible to burning. CONCLUSIONS: The data lend limited support to the hypothesis of increased risk associated with intermittent UV exposure. The findings suggest that future studies should take age at diagnosis, host susceptibility and histological subtype into account.