This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders.Subjects were 1583 residents aged 50–65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activity  were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 protein serum levels, number of micronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxy-deoxyguanosine in urine. Confounding factors were taken into account.Overall significant differences between areas were found for carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around waste incinerators, in the cities of Antwerp and Ghent, in industrial areas and also in other rural areas. Within an industrial area DNA strand break levels were almost three times higher close to industrial installations than 5 kilometres upwind of the main industrial installations (p < 0.0001). Positive exposure-effect relationships were found for carcinoembryonic antigen , micronuclei (PCB118), DNA damage (PCB118) and 8-hydroxy-deoxyguanosine . Also, we found significant associations between values of PSA above the p90 and higher values of urinary cadmium, between values of p53 above the p90 and higher serum levels of p,p'-DDE, hexachlorobenzene and marker PCBs  and between serum levels of p,p'-DDE above the p90 and higher serum values of carcinoembryonic antigen. Significant associations were also found between effect biomarkers and occupational or lifestyle parameters.Levels of internal exposure, and residence near waste incinerators, in cities, or close to important industries, but not in areas with intensive use of pesticides, showed positive correlations with biomarkers associated with carcinogenesis and thus probably contribute to risk of cancer. In some rural areas, the levels of these biomarkers were not lower than in the rest of Flanders. Flanders is one of the most densely populated areas in Europe, with intensive traffic, industrial activities and intensive farming close to habitation. The pilot Flemish Environment and Health Survey (FLEHS) showed differences in internal exposure to pollutants in function of area of residence and indicated that small differences in pollutant levels were associated with observable differences in effects -4. Theseet al. [et al. [et al. [This program comprised measurements of internal exposure on each of these age groups. Concerning the neonates, follow-up studies concerning neuropsychic development, asthma and allergy were performed. Concerning the adolescents, effect biomonitoring comprised measurements of hormone levels in boys and sexual maturation of boys and girls. For adults, effect biomonitoring entailed genotoxic tests and measurements of tumor associated protein levels (reported in the present paper) and also measurements of the expression of selected genes. Also, for both adolescents and older adults a study was performed on the relationship between carcinogenesis-related biological effects and 36 polymorphisms in 23 genes involved in xenobiotic metabolism, DNA repair and oxidative stress. This biomonitoring program (2002–2006) already resulted in several publications: internal exposure to pollutants in adolescents was described by Schroijen et al. ; dietary [et al. . A detai [et al. . SeveralHere we report our observations on cancer-related markers of biological effects in 50 to 65 year old adults. Because of the important role of somatic mutations in carcinogenesis , we inclOur project also intended to test the hypothesis that low levels  of internal exposure to pollutants known or suspected to cause cancer were associated with increases in levels of oxidative DNA damage, of DNA strand breaks, of micronuclei or of tumor associated proteins.2 mainly under the wind of a waste incinerator. For comparison we included 'rural areas'. These rural areas are, in Flanders, certainly not devoid of environmental pollution and might (see discussion) even show some higher exposures [As areas with a high level of pollution stemming from heavy industry, the port areas of Antwerp ('Antwerp port') and Ghent ('Ghent port'), and the 'Albert canal' and 'Olen' industrial basins were chosen. At the start of the project the ports of Antwerp and Ghent were considered together as one industrial zone, but in view of differences in type of industry and in view of the results obtained (e.g. for the adolescents ), we thoxposures ,23 due txposures . However2, corresponding to 22% of the total surface of Flanders . The 65 selected municipalities correspond to 20% of the total Flemish municipalities. Except for 'rural Flanders' and for 'waste incinerators', all study areas were contiguous geographical entities.Table A Stratified Clustered Multi-Stage Design was used to select 775 men and 808 women (n = 1583) aged 50 to 65 as a random sample of the population of the areas under study. In the selected areas approximately 1.2 million inhabitants are living which is 20% of the Flemish population. A sample size of 200 participants per study area was aimed at because a power calculation demonstrated that this appears to be statistically sufficient to detect differences of 20% in internal pollutant concentrations between study areas. As the port area was further split in two different study areas, the sample size was lower in the individual port areas of Antwerp (n = 163) and Ghent (n = 36). Sampling took place in three steps: first by study area, secondly by sub-municipality entities for access to participants, and thirdly by selection of the participants in accordance with the inclusion criteria.Height and weight were measured, body mass index (BMI) was calculated. 200 mL of urine and 40 mL of blood were collected from each participant. Immediately after sampling, serum was separated. Samples of serum, whole blood, and urine were stored at 4°C for maximum one week, or immediately deep frozen. All laboratory analyses were performed, using blinded methods, in specialized laboratories that met national and international quality-control standards.A self administered questionnaire was used to collect information on physical condition, use of medication, education, professional exposure to various pollutants , housing conditions, pesticide use, exposure to noise and traffic, quality and quantity of homegrown, local and other food consumption, alcohol consumption and smoking. On the basis of these questionnaires a number of parameters were calculated, including average amount consumed per day of fruit, vegetables, meat fat, fish fat and dairy fat. Other parameters concerned self-caught freshwater fish, recent and lifetime tobacco consumption, recent and average alcohol consumption, and indices for general indoor housing quality, exposure to traffic, to indoor and outdoor stoking of diverse organic materials and for experiencing nuisance from noise during the day and during the night. Smoking was quantified in terms of units  smoked during the entire lifetime. For people 50–65 years of age, 15 cigarettes a day corresponds roughly to 200.000 units over a lifetime.Measured exposures included blood cadmium (μg Cd/l), urinary cadmium (μg Cd/g creatinin), blood lead (μg/l), serum hexachlorobenzene (ng HCB/g lipid), serum p,p'-DDE (ng/g lipid); serum polychlorinated biphenyls (PCBs): PCB 99, PCB 118, PCB 170, PCB 138, PCB 153, PCB 180 (ng/g lipid); serum Calux TEQ ; a biomarker for PAH exposure, 1-hydroxypyrene in urine ; and a biomarker for benzene, t,t'-muconic acid in urine .et al. [Lead and cadmium concentrations in whole blood were determined after an acid digestion pre-treatment destroying the organic matrix and a ten times dilution, followed by High Resolution – Inductively Coupled Plasma – Mass Spectrometry detection (ICP-MS) as described by Schroijen et al. . DetectiPCBs, HCB and p,p'-DDE were analyzed using gas-chromatography/electron capture detection (GC-ECD) . 2 mL of1-Hydroxypyrene , and t,t'-muconic acid  were detected in urine based on methods used by Angerer & Schaller . The detet al. [et al. [n-hexane and dried on a Celite/Na2SO4column. The extract was then transferred on an Acid Silica column in series with an activated Carbon column (XCARB column). After elution of the sample with n-hexane, the acid silica column was discarded and the XCARB column was then differentially eluted to yield 3 fractions:CALUX analyses of dioxin-like activity in blood plasma was performed as described by Van Wouwe et al.  and Schr [et al. . Brieflyn-hexane/acetone allows the elution of some toxic or interfering compounds1. a mixture of n-hexane/toluene/ethyl acetate2. the PCB fraction is eluted with a mixture of 3. the PCDD/F fraction is collected with 20 mL of toluene.After this clean-up, fractions 1 and 2 were discarded and only the dioxin fraction was used for the bio-analysis. The solution containing the dioxins was then evaporated and exposed to the mouse hepatoma H1L6.1 cell line developed by Xenobiotic Detection System, Inc. After an exposure time of 20 h, cells were lysed and measurements were made with a luminometer. TEQ-values were calculated after comparison of the obtained signals to a 2,3,7,8-TCDD calibration curve.The following is a summary of the data on which our selection of biomarkers of effect was based.Increased serum levels of Prostate Specific Antigen (PSA) are found in the vast majority of men with prostate cancer. A Finnish study found, for men under 65 years of age, a sensitivity of 93% and a specificity of 96% for PSA as a diagnostic test for prostate cancer using a limit value of 4 ng/mL . Serum PSerum levels of Carcinoembryonic Antigen (CEA) are increased in many types of cancer, in smokers and in persons exposed occupationally or environmentally to pollutants -33. SeruIncreased serum levels of mutated p53, or of anti-p53 antibody, have been found in cancer patients  and in wMeasurement of the number of micronuclei per 1000 binucleated peripheral blood cells (micronuclei) is one of the best established biomarkers of chromosome damage . An incrMeasurement of DNA-strand breaks in peripheral blood cells in terms of the median value of the percentage of DNA in the tail using the comet assay was selected to reflect recent damage to DNA. The alkaline single-cell gel electrophoresis (SCGE) or Comet assay is an easy, reliable and rapid method to detect DNA single strand breaks, alkaline labile sites and delayed repair sites of DNA. It is able to detect low levels of DNA damage, requires small sample sizes and has a rather low cost . The intThe measurement of 8-hydroxy-deoxy-guanosine (HDG) in urine per gram creatinine was selected to assess recent oxidative stress. HDG is excreted in the urine after excision of this mutagenic oxidative adduct from DNA and reflects the amount of oxidative damage to DNA and its repair. Its measurement is affordable and has inter- and intra-assay coefficients of variation of 8 to 24% . We esti® 2000  technology was applied on 15 and 10 μl serum samples respectively, that were assessed within 24 h after venipuncture. The within-run precisions of the methods applied on samples in the normal, non-pathological range were 3.0 and 3.3% (coefficients of variation) respectively. p53 levels were analysed in 100 μL serum samples with the TiterZyme EIA p53 Kit  in accordance with the manufacturer's instructions. The lower limit of detection  was determined on the basis of the mean of the zero standard  plus two standard deviations, and calculated to be 9 pg/mL. The monoclonal capture antibody recognizes both wild-type and mutant human p53. p53 results below the detection limit were given the value of 4.5 pg/ml.Tumor associated protein levels in serum were measured by Interlab,  a laboratory recognized by the Belgian Ministry of Health as a reference laboratory for tumor markers. CEA and PSA serum concentrations were both measured with an immunometric assay. The Immuliteet al. [®, Methasystems inc. For each person 30% of the slide was viewed. Around 200 cells were processed and the median percent of DNA migration in the tail area was determined and used as a measure of DNA damage. As positive control one slide with nuclei from deep frozen whole blood cells was added to each electrophoresis chamber. In those positive controls at least 30% of DNA had to migrate into the tail area to control the functioning of the electrophoresis.The amount of DNA-strand breaks was evaluated by the alkaline comet assay as described in Verschaeve et al. . The whoThe cytokinesis-block micronucleus assay was performed on whole blood cultures from 100 individuals using standard procedures . For eacUrinary HDG, a measure for oxidative DNA-damage, was measured via ELISA using the competitive inmunosorbent assay-kit .Statistical analyses were performed with the Statistica 7.1 program . The effect parameters did not show a Gaussian distribution, so the natural logarithm of these parameters was used in statistical analysis. Crude data (median and p10 and p90) as well as adjusted data are shown. As we did in our previous studies ,23, we uAlso, effect biomarker levels of each area were compared to the rest of the dataset. The correlation of biomarkers of effect (as dependent variables) with the measured parameters of internal exposure and with some exposure variables derived from questionnaires was studied in simple linear regression. When this analysis resulted in a p-value below 0.05, a multiple regression was performed with the biomarker of effect as dependent variable and, as independent variables, in addition to the parameter of exposure in question, also the relevant confounding factors.Some sets of effect and exposure biomarkers showed, in a bivariate regression plot, contrasting correlations for different ranges of exposure or effect. In those cases we used p10, p25–p75 and p90 levels to discriminate classes of exposure or effect in order to study correlations in the different ranges using AN(C)OVA.ex defined as the arithmetic mean of the z scores for blood lead concentration, sum of serum concentrations of marker PCBs , serum concentration of PCB 118 (considered to reflect exposure to dioxin-like PCBs [ex = (zblood lead + zsum of serum marker PCbs + zPCB118+ zHCB + zDDE + zdioxin-like activity + zurinary Cd + z1-OHP + zttMA)/9).We calculated for each biomarker of exposure a standard or z score for each individual by dividing the difference between the value for that individual and the mean value for the entire subject population by the standard deviation for the entire subject population. We calculated for each subject an index of internal exposure Iike PCBs ), HCB anTable Table After correction for confounding factors, overall differences for effect biomarker levels between areas were observed for CEA, micronuclei, DNA-strand breaks and oxidative DNA damage . Compared to the rest of the dataset, significantly higher values of biomarkers of effect were observed for residents of 'waste incinerators'  and Ghent (DNA-strand breaks). Compared to the area with the lowest observed value, significantly higher values were observed for persons residing near waste incinerators , in Antwerp , in Ghent , in the 'rural area' , in the 'Albert canal' area (micronuclei), in the 'Olen' area (micronuclei) and in the 'fruit area' (oxidative DNA damage).After additional correction for nutrition, alcohol consumption and education, overall significant differences between areas were still observed for oxidative DNA damage (p = 0.040) and for DNA-strand breaks (p < 0.001), but p-values increased for CEA (p = 0.16) and for micronuclei (p = 0.11).Within the main areas differences were observed (after correction for confounding) between small local districts. Between the areas around the different waste incinerators significant differences were observed for DNA-strand breaks (p < 0.0001) with values  of residents around the incinerators of Menen , Roeselare  and Wilrijk  significantly higher than those of Harelbeke . Within 'Antwerp port' a significant overall difference for DNA-strand breaks (p < 0.0001) was found, with values in Burcht, close to a large non-ferro industry  significantly higher than Beveren situated about 6 kilometres upwind of the mean industrial installations . For 'rural area' significant overall differences were found for CEA (p = 0.03) with significantly higher values  in the rural areas around Brakel  as opposed to those around Eeklo .ex), Micronuclei (PCB118), DNA-strand breaks measured through the comet assay (PCB118) and oxidative DNA-damage assessed through measurement of HDG in urine .Table Some sets of effect and exposure biomarkers showed, in a bivariate regression plot, a correlation that was dependent on the range of exposure or effect and was significant after correction for confounding factors.- Higher PSA levels (above p90) were associated with higher values of urinary cadmium p = 0.029), as is shown in figure 9, as is ex , as is shown in figures - Higher p53 levels (above p90) were associated with higher values of marker PCBs, DDE, HCB and the index of internal exposure I- Higher DDE levels (above p90) were associated with higher CEA levels (p = 0.018), as shown in figure - Higher levels of blood and urinary cadmium above p90) were associated with lower micronuclei counts compared to the group between p25 and p75 of cadmium concentrations (p = 0.037 and 0.033 respectively). Lower levels of blood and urine cadmium (below p10) were associated with lower counts of micronuclei compared to the group with cadmium concentrations between p25 and p75, although this was not statistically significant. See figures 0 were asTable Significant negative associations were found for DNA-strand breaks as measured with the comet assay with daily consumption of meat fat and occasional consumption of self-caught freshwater fish.Between smoking and number of micronuclei a complex relationship was observed figure . OverallLevel of education was not significantly associated with effect biomarkers.As in the pilot campaign of the Flemish human biomonitoring program ,4,23 we 2 is increased above the risk of the rest of the Flemish population by the heavy industry situated in those areas. This may in part be explained by the fact that many participants resided in zones located to the west of the industrial sites in both port areas. The dominant wind pattern in Belgium is from west to east, which means that residents living west of the point sources are less exposed. Within 'Antwerp port', the district of Burcht situated close to a large non-ferro industry showed much more DNA-strand breaks than the district of Beveren situated about 6 kilometers further to the west of the industrial sites. Our findings suggest that a detectable increase in risk might be restricted to those groups, such as the inhabitants of Burcht, residing within a few kilometers of important point sources.In the 'Olen' and 'Albert Canal' industrial areas micronuclei values were significantly higher than in the area with the lowest value, suggesting that both petrochemical and non-ferro industries might contribute to the risk of cancer of people residing in their vicinity. However we found no evidence indicating that the risk of cancer of the whole population of large areas of the order of 200 kmOur observations indicate that residence near waste incinerators might be associated with an increase in the risk of cancer. Indeed, all three biomarkers of genotoxic effects were significantly increased, not only above the level observed in the area with the lowest value, but also above the level observed for the rest of Flanders. For each of these biomarkers the highest level was observed in residents of 'waste incinerators'. In addition, the level of CEA was above the level observed in the area with the lowest value.Our observations also suggest that residence in cities might be associated with some increase in the risk of cancer. Both in Antwerp and in Ghent levels of CEA and of micronuclei were significantly elevated above the level observed in the area with the lowest value. In Ghent DNA strand breaks were increased compared to the level observed in the area with the lowest value, as well as above the level observed in the rest of Flanders.Interestingly, we found no evidence that residence in an area where intensive use of pesticides occurred, increased risk of cancer. On the contrary, although the level of oxidative DNA damage observed for these residents was significantly increased compared to the level observed in the area with the lowest value, the levels of micronuclei, of DNA strand breaks, of CEA and of PSA were significantly lower than those observed for the rest of Flanders. In terms of our observations, the 'fruit area' appeared to be the area with the most favorable results.et al. [Remarkably, results for rural Flanders were not significantly better for any of the biomarkers of effect than for the rest of Flanders. For micronuclei and DNA-strand breaks, relatively high values were observed, significantly elevated above those observed in the area with the lowest value. Correspondingly, relatively high levels of internal exposure to some pollutants were observed in residents of rural areas in Flanders in both the pilot and the subsequent biomonitoring studies in Flanders. Indeed, in the Flemish pilot biomonitoring study, women aged 50–65 residing in the rural area of Peer had higher levels of cadmium and dioxin-like activity in their blood or serum, and higher levels of cadmium and 1-hydroxypyrene in their urine than women residing in the city of Antwerp . Also, aet al. ).et al. 2007; unpublished results) or more intense biological effects  near point sources of pollution reaching marginal or even full statistical significance, although only a low number of people were studied around these point sources. In terms of DNA strand breaks, a difference of almost a factor of three was observed. This suggests that the relatively high values of internal exposure measured in most people in Flanders, independent of their area of residence, are in part due to emissions of point sources. Although they do not lead to detectable increases in internal exposure nor to detectable biological effects in the larger area where they are located, they do lead to significantly higher internal exposure and associated biological effects in people residing at short distance. Distance from nuclear power plants showed a pronounced negative correlation with childhood leukaemia in a recent German study [Our study was not designed to detect differences in internal exposure or in biological effects in the immediate surroundings of sources of pollution, and was only meant to observe differences between large areas with different types and levels of pollution. However, we did observe higher internal exposure (Schroijen an study .Our results indicate that levels (see table Higher prostate specific antigen (PSA) levels (above p90) were associated with higher cadmium levels in blood. A positive association between internal exposure to cadmium and increased serum PSA values has been found previously -57. Incret al. [We found positive associations between several parameters of internal exposure and carcinoembryonic antigen (CEA) levels. This was the case for urinary cadmium, blood lead, serum DDE, urinary ttMA, urinary 1-OHP levels and for an index for internal exposure. Also smoking, alcohol consumption and consumption of fish fat, and occupational exposure to solvents or to halogenated hydrocarbons showed a positive association with serum CEA levels. In our pilot study we already found a positive association between serum CEA and an index of internal exposure based on blood levels of lead, marker PCBs and dioxin like activity, and on urinary levels of cadmium and 1-OHP . Positivet al.  and Herbet al. . Also, Het al.  reportedet al. . Also, eet al.  or coloret al. .et al. [In our dataset serum levels of the tumorsuppressor protein p53 above the p90 were associated with higher levels of marker PCBs, DDE, HCB and an index of internal exposure. Howsam et al.  found a et al. . Increaset al. ,14,71,72et al.  and PAHset al. ,38. Antiet al. . Levels et al. ,41.et al. [et al. [et al. [et al. Concerning the observed positive association between level of micronuclei and consumption of vegetables, we did not find such an association in published data. On the contrary, there are many reports on a possible protective effect of a high consumption of fruit and vegetables against DNA-damage [et al. [et al. [et al. [Levels of micronuclei showed a positive association with higher levels of PCB 118 in serum and with a higher consumption of fish fat and vegetables. According to Park et al.  total diet al. ,74. A poet al. . Consist [et al.  found th [et al.  found thA-damage . So it i [et al.  in pesti [et al.  also fou [et al.  hypotheset al. [As stated by Møller et al.  the comeet al. ,81. Althet al. . Burninget al. . Burninget al. -85. As tet al. , and conet al. ,87. So, et al. .8-Hydroxy-deoxy-guanosine (HDG) results from oxidation of the guanine-residue of DNA. HDG levels were higher in subjects with a higher internal exposure to benzene and polycyclic aromatic hydrocarbons as assessed through urinary levels of ttMA and 1-OHP respectively. This was also observed by other authors . BenzeneAlthough we found the levels of genotoxic parameters and of tumor-associated proteins quite homogenous in Flanders, residence near waste incinerators, in cities, or close to important industries showed a positive correlation with biomarkers associated with carcinogenesis. Thus, residence in those areas probably contributed to the risk of cancer. Whereas for the 'fruit area' with intensive use of pesticides favourable results were obtained, in some other rural areas the levels of these biomarkers were not lower than in the rest of Flanders. In addition, we observed more intense biological effects occurring in persons residing near point sources of pollution. This suggests that the relatively high values of internal exposure measured in most people in Flanders, independent of their area of residence, are in part due to emissions of point sources, the effects of which, in terms of both internal exposure and biological effects, can only be detected in people residing at short distance. Levels of internal exposure occurring in the general population in Flanders showed positive correlations with biomarkers associated with carcinogenesis and probably contributed to the risk of cancer.ex: index of internal exposure; p53: p53 protein in serum; PAHs: polyaromatic hydrocarbons; PCB: polychlorinated biphenyls; PCDD/F: Polychlorinated Dibenzo-p-Dioxin/Polychlorinated Dibenzofuran; PLSD: Phisher protected least significant difference; PSA: prostate specific antigen; SCGE: single cell gel electrophoresis; TEQ: toxic equivalent; ttMA: t,t'-muconic acid1-OHP: 1-hydroxypyrene; ANCOVA: analysis of covariance; ANOVA: analysis of variance; BMI: body mass index; Cd: cadmium; CEA: carcinoembryonic antigen; crt: creatinin; FLEHS: Flemish Environment and Health Survey; GC-ECD: gas chromatography – electron capture detection; HCB: hexachlorobenzene; HDG: 8-hydroxy-deoxy-guanosine; HPLC: high performance liquid chromatography; ICP-MS: inductively coupled plasma – mass spectrometry; IN. van Larebeke has worked occasionally as a consultant for the World Wide Fund for Nature and presently works occasionally as a consultant for Veolia Inc, active in environmental services and waste management.The other authors declare that they have no competing interests.NvL, GS, WB, VN and LB contributed to the conception and design of the study, VN, EVDM, MB, GK, MB and EDH contributed to the field work and acquisition of data, SDC and LB contributed to the analysis of the data. SDC did the literature study, SDC and NvL wrote the manuscript. All authors read and approved the final manuscript.


P = .023), skin involvement (P = .003), and stage at presentation (P = .004) were significantly associated with overall survival. Skin involvement at presentation (P = .003), T size (P = .09), lymph node status (P = .013), and stage (P = .003) were strong predictors of relapse-free survival. Patients had a 5-year survival of 78%, compared to 64% of breast cancer patients diagnosed between 1996 and 2002 identified in our previously published study. Thus, despite Omani breast cancer patients continuing to present with advanced breast cancer, survival rates have significantly improved.Breast cancer is the leading cause of cancer-associated mortality in women, with elevated incidence in developing countries. This retrospective study included all 122 patients diagnosed with breast cancer from January 2003 to December 2008 in the Sultanate of Oman. Age at presentation was 47.41 years (SD±12.88), with one-third of patients younger than 40 years. The majority of patients presented with stage III (41.2%) and IV (18.2%) breast cancer. T size ( Breast cancer is the leading cause of cancer-related mortality in women worldwide. Almost half of annually diagnosed females with breast cancer belong to developing countries, where they present at a younger age with advanced-stage disease. These women also have poor overall outcomes compared to women in developed countries. The advanced stage of presentation of breast cancer in developing countries was attributed to a lack of mass education and screening programs, poverty, poor access to health care facilities, lack of expertise, and poor country infrastructure –7.It is an established fact that ethnic disparities affect breast cancer outcome. Despite correction of well-known factors associated with breast cancer-related outcome, such as tumor size, lymph node status, hormone receptor expression, Her2/neu gene expression, stage, and age at presentation, racial differences were prominent as prognostic factors and have been associated with genetic differences between races. Investigators have proposed multiple reasons to explain these differences between races , 8–12. The Sultanate of Oman is a developing Asian country in the Gulf Region with a developing health care system. Like women worldwide, Omani women also share major burden of breast cancer incidence and associated mortality. One out of five Omani women is diagnosed with breast cancer in her lifetime, and the age-standardized incidence rate is 15.6 per 100,000. In our last reported study, we found that age at diagnosis is younger in Oman than in the western world, and the majority of patients present at advanced stages of disease (III and IV) [In our last study, we reported the clinicopathologic features, such as treatment modalities, outcome, and associated prognostic factors for Omani women, that have a diagnosis of breast cancer between the years of 1996 and 2002. The results of this previous study revealed that patients in Oman presented at a younger age and with an advanced stage of disease. Furthermore, there is an underutilization of neoadjuvant (NA) therapy with 5-year relapse-free survival (RFS) and 5-year overall survival (OS) of 64% and 62%, respectively [We analyzed patient data using the computerized hospital information system of our university hospital for patients admitted with the diagnosis of invasive breast cancer from January 2003 to December 2008. Our hospital  is one of the two main hospitals providing cancer treatment in the Sultanate of Oman. Among the patients included in this retrospective data, the majority were diagnosed and treated in this hospital, but some patients presented either after being diagnosed in other hospitals or after undergoing surgery at peripheral hospitals. Our pathology department reviewed almost all histopathological specimens for confirmation of diagnosis and immune staining of tissue for estrogen receptor (ER), progesterone (PgR), and Her2/neu status. Due to the advanced stage of breast cancer at presentation, the breast cancer stage in most patients was determined by CT scans of the chest, abdomen, and pelvis, as well as with bonescans.The records of all patients with a confirmed diagnosis of invasive breast cancer were reviewed, and a database was created. Variables were identical to those presented in our previous published study and included age and sex; date of diagnosis; side of involved breast; histopathological type of tumor; clinical and pathological tumor size; pathological or clinical involvement of skin or nipple areola complex; clinical and pathological lymph node involvement; tumor grade; marker status of tumor, including ER, PgR, and Her2/neu status; clinical and pathological stage of the patients. Records were also reviewed for the date of last followup exam, date and site of relapse, and date of death, when relevant. Relapse-free survival (RFS) was measured from diagnosis to the date of documented relapse and was censored at the date of last followup. Overall survival (OS) was measured from the date of diagnosis to the date of death and censored by the last date of followup. P-values herein are nominal 2-sided. Data analysis was performed using SPSS version 16.Kaplan-Meir curves were used to determine OS and RFS and the log-rank test was used for comparison analysis. The Cox proportional hazard model was used for univariate analysis with the variables included being age, menopausal status, tumor size, lymph node status, tumor grade, and estrogen receptor status. The Cox model was used for multivariate analysis including all statistically significant factors as per univariate analysis. All reported A total of 122 patients were identified with a diagnosis of invasive breast cancer. The majority of patients were of Omani origin 108 (88.5%). The mean age of all patients was 47.41 (SD ± 12.88) years and 3 of 122 patients were male . Almost External beam radiotherapy was administered to 73.8% of patients. All patients were treated locally, differing from our previous paper due to the fact that radiation facilities were not available in Oman at the time. With a mean followup duration of 54 months, 27 patients died, and 4 patients were lost to followup. Among the patients that died, 10 deaths were of the metastatic group and 17 were of the nonmetastatic group. Among the 33 patients who experienced a relapse, 18 of those patients subsequently died from their disease. In nine patients, disease relapse led to bone metastases, and five patients had brain metastases; lungs, pleura, liver, and local relapse were also manifestations identified at the time of disease recurrence. Seventy-six patients were living at the end of the study, with no evidence of disease. Additional 15 patients have experienced persistent disease, with 12 of those 15 patients belonging to the metastatic group.P = .003), T size (P = .023), and stage (P = .004) were significant factors associated with OS as determined by univariate analysis. Additionally, skin involvement at presentation (P = .003), T size (P = .09), lymph node status (P = .013), and stage (P = .003) were strong predictors associated with RFS (P = .006) for OS, as determined by multivariate Cox regression analysis. Skin involvement at presentation  years. Significantly, this age at presentation is almost a decade younger than women who present with invasive breast cancer and are from developed countries. In contrast, the age at presentation in the present study is relatively consistent between Oman and other developing countries, including neighboring Arab countries –15. HoweNA chemotherapy administered to patients for locally advanced breast cancer is generally accepted as the treatment of choice. This type of treatment is the reason for the increasing number of breast-conserving surgeries (BCSs) and is also associated with better OS –20. HoweWe noticed better 5-year survival in patients of this present study, in which patients had a 5-year OS of 78% as compared to 64% in our last study  though dPresentation at an advanced stage is common among patients with breast cancer in undeveloped countries. Socioeconomic issues, cultural barriers, and low literacy rates have been reported as the factors responsible for advanced stage of presentation, in addition to lack of screening programs and poor access to health care facilities , 14, 15. In conclusion, although the number of patients in this study is relatively small, the study results show that patients in Oman still present with advanced stages of disease at a relatively young age. However, breast cancer patients enrolled in the present study have markedly improved RFS and OS. The improvement in RFS and OS is most likely due to utilization of various treatment modalities, including updated chemotherapy protocols and the use of trastuzumab. Further comparisons between this and the previous study reveal that Omani breast cancer patients still present with advanced disease, poor tumor differentiation, at a young age, and have a low percentage of hormone-positive tumors, all of which are known factors associated with poor overall disease outcome. Mass education programs, health awareness measures, and establishing screening programs are basic ways to decrease the disease burden and enable diagnosis at earlier stages of disease.


This cross-sectional study was conducted to investigate the prevalence and predictors of overweight and obesity by location of residence among randomly-selected 2,577 urban school girls aged 12–17 years in Rasht, Iran. Data on age, frequency of skipping breakfast per week, physical activity, hours of television viewing, self-perception about body condition, and home address were collected. Birthweight of the girls, educational levels of parents, weights and heights of parents, and employment status of mothers were asked to the parents using a self-administrated questionnaire. The overall prevalence of overweight and obesity in this population was 18.6% and 5.9% respectively. Overweight or obesity was more common among girls from low-income areas compared to high-income areas . Maternal education was positively related to overweight/obesity of the girls. Results of logistic regression analysis showed that risk of overweight/obesity was higher in girls whose either parent was overweight or obese. Furthermore, living in low-income areas and skipping breakfast were independently related to overweight/obesity. These data suggest that overweight and obesity are a public-health concern among school girls, especially in low-income areas in Rasht. Knowing risk factors in population subgroups is important for planners in the country because it helps target interventions. Overweight and obesity are rapidly increasing among children and adolescents in developing countries , 2. AdolIran is a middle-income country, experiencing rapid epidemiological transition , and theThe main objective of this study was to provide current data on the prevalence of overweight and obesity among school girls by location of residence, socioeconomic status, and maternal educational levels in Rasht. We also aimed at exploring contribution of some lifestyle factors to these differences in this population.The study was designed to evaluate the current status of overweight/obesity by location of residence and its correlates among school girls in urban areas of Rasht in northern Iran. The study population was school girls aged 12–17 years living in Rasht, the main city of Guilan province. During October 2006–March 2007, 2,610 school girls were randomly selected from low- and high-income areas in Rasht with no exclusion criteria. Rasht city was divided into five areas based on the type and price of house. One area known for its luxury houses where the rich live was considered a high-income area, and two areas where price of house was lower compared to other areas were considered low-income areas in this study. Twenty-five schools from low-income areas and 15 schools from high-income areas were randomly selected. Ten percent of students in each class were systematically selected using the class list. Selection of students was initially made by level of education (class), not by age. Since the age of 33 students was not in the range of the study protocol, they were excluded, and 2,577 observations were included in data analysis.th percentile of the World Health Organization cut-offs. Parental overweight and obesity was defined as BMI equal or greater than 25 kg/m2 and 30 kg/m2 respectively.Data on age, frequency of skipping breakfast per week, physical activity, hours of television viewing or video game, birth-rank, self-reported body-weight, self-perception about body condition, and home address were collected using a self-administrated questionnaire. Information on birthweight of the girls, parental education levels, and employment status of mothers was gathered through a self-administrated questionnaire given to the parents. Original weight (defined as body-weight before getting married) and current body-weight and height of parents were self-reported. Frequency of breakfast was recorded by asking the question: how many times during a week do you take breakfast? Response categories were ‘seldom’ and ‘most times per week’. Self-perception about body condition was evaluated by asking “How do you think about your body-weight? The responses were categorized as ‘overweight’, ‘normal weight’, and ‘I have no idea’. A questionnaire on physical activity was also developed for the study that asked the participants to recall the number of hours per week if they had participated in any structured physical activity or team sport in the last six months. Response categories ranged from 0 to 8+ hours per week. The participants were asked about the time spent in commuting between home and school under five time-categories, such as less than five minutes per day, 5–15 minutes per day, 15–30 minutes per day, 30–45 minutes per day, and more than 45 minutes per day. Time spent in television watching and computer/video games was recorded for each day of a typical week and divided into three time-categories, such as <3 hours per day, 3–5 hours per day, and >5 hours per day. Anthropometric measurements of the girls were performed in light dress and without shoes in the morning. Body-weight was measured to the nearest 0.1 kg using a balanced-beam scale, and height was measured to the nearest 0.5 cm with the girls standing up and head, back, and buttock on the vertical land of the height-gauge. Self-reported body-weight of the girls was categorized as ‘I do not know’, ‘correct’ (if the reported weight was ±2 kg of the measured body-weight), and ‘incorrect’. Age and sex-specific body mass index (BMI) cut-offs, proposed by the International Obesity Task Force (IOTF), were used for defining overweight and obesity . UnderweThe differences in the prevalence of overweight and obesity were tested using chi-square statistics. In data analysis, level of education of mothers was classified as less than five years of schooling, 5–11 years of schooling, high school diploma (12 years schooling), and college study (>12 years of schooling). Employment of mothers was classified as housewife or employed. Logistic regression analysis was used for determining the predictors of overweight and obesity among the study girls.Values were given as mean and 95% confidence intervals. The p values less than 0.05 were considered the level of significance. Analyses were performed using the SPSS software (version 10.01) for Windows .All the parents gave written consent for participation in the study. The Ethical Committee of the Guilan University of Medical Sciences approved the study protocol.The mean values of BMI and the prevalence of overweight and obesity among the girls as a function of age, maternal education, and location of residence are presented in Overweight and obesity among mothers were 43.2% and 27.3% respectively. Overweight and obesity among fathers were 43.3% and 12.3% respectively. Specific weight gain after marriage was reported by 2,113 mothers and 1,984 fathers respectively. The mean weight gain by mothers and fathers was reportedly 15.3±10.4 and 10.4±9.4 kg over a 8–15-year period respectively. The The results of logistic regression analysis showed that risk of overweight/obesity among the school girls were independently related to parental overweight/obesity, location of residence, and skipping breakfast .The prevalence of overweight and obesity is already high among Iranian women, and it ranged from 55% to 75% in different parts of Iran . Results! The present study has shown that the girls living in low-income areas were more prone to overweight or obesity than were the girls living in high-income areas. On the other hand, overweight and obesity were positively related to maternal education. Our findings showed that more-educated women were more likely to reside in low-income areas. In Iran, standard of living is low due to international sanctions and internal inflation, and many well-educated people have no employment opportunities (Studies in developed countries have demonstrated a negative relationship between socioeconomic status and overweight among adolescents , 7. Thertunities . In multIt has been previously reported that there is less social pressure for conforming to an ideal perception about body condition in Iran, an Islamic country . IranianThe results of this study indicate that, when a broad range of factors were taken into consideration simultaneously, skipping breakfast, location of residence, and parental overweight and obesity had the largest association with overweight/obesity in these high school girls. Skipping breakfast has been reported to be associated with overweight/obesity in children , 22 but Weight status of parents and especially maternal overweight have been reported to be related to overweight/obesity in adolescents in Western countries , 26. TheThere are no data on the physical activity patterns of Iranian adolescent girls. Results of a study showed that activities during leisure are extremely low among Iranian adult women due to religious reasons and lack of recreation facilities . The resThere are possible limitations to this study. Parental body-weight and height were self-reported in this study while there are no data to show whether self-reported weight and height is reliable in Iran. Besides, no direct data on economic status, i.e. income, were collected in this study.In conclusion, chronic diseases, including CAD and diabetes, are the main causes of mortality in Iran . AvailabThis work was financially supported by the Guilan University of Medical Sciences, Rasht, Iran. The authors thank the students and their parents for their participation in the study. The authors appreciate the school personnel for their cooperation in collecting the data.


The belief that adolescents engaged in sports increase their overall physical activity level while simultaneously decreasing physical inactivity has been the foundation of many intervention programs in developing countries. The aim of this study was to analyze the association between regular participation in sports and both active behaviors and TV viewing during leisure time.A total of 1752 Brazilian adolescents  participated in this study. Regular participation in sports, as well as active behaviors  and TV viewing during leisure time were assessed by means of a questionnaire. The chi-square test analyzed the association between sports practice and leisure time behaviors, and the Poisson regression with robust variance indicated the magnitude of these associations.The prevalence of regular participation in sports was 14.8% . After adjustment for all confounders, participation in sports was associated with, at the highest frequency, cycling (PR = 2.55 [1.80–3.60]) and walking (PR = 2.69 [1.98–3.64]) during leisure time. However, there was not an association between the participation in sports and frequency of TV viewing (PR = 1.28 [0.81–2.02]).This study presented data indicating that the regular participation in sports is positively associated with a higher frequency of physically active behaviors during leisure time. However, the results did not support the hypothesis that the engagement in sports necessarily decreases leisure time spent in TV viewing. In recent decades, physical inactivity has become one of the most pressing public health problems among both developing and developed countries ,2. HowevPhysically active children and adolescents who engage in sports are more likely to be physically active during early adolescence and adulthood, respectively ,8. Thus,It is usually accepted that media-based sedentary behaviors such as television viewing (TV viewing), surfing the internet, and playing video games consume time that might otherwise be spent in physical activity. Furthermore, these sedentary behaviors may promote snacking between meals , which iAmong adolescents, TV viewing is considered an important indicator of sedentary behaviors because in both developed and developing countries the number of televisions per person increased positively with the rate of overweight . NeverthThis possible dissociation between PA and TV viewing has obvious relevance for public health, because, if it were actually the case, the design of health-promotion strategies should be drastically altered. Such strategies, then, would not only have to increase PA during childhood and adolescence, but also develop separate mechanisms for decreasing time spent in TV viewing. Hence, due to the scarcity of data regarding the existence and degree of this dissociation, it is necessary to discover the interrelation of these variables, thereby facilitating the creation of better informed intervention programs.Thus, the primary hypothesis of this study was that higher participation in sports would be positively associated with an elevated frequency of other active behaviors during leisure time. The secondary hypothesis, then, was that the engagement in sports would be also be positively associated with a decreased frequency of TV viewing.The presented study analyzed the relationship between regular participation in sports and both TV viewing and active behaviors  during leisure time in a sample composed of Brazilian adolescents.This cross-sectional study was carried out in the city of Presidente Prudente (HDI = 0.846), Southeastern Brazil, from July to October 2007. The city of Presidente Prudente is located in the western part of the state of São Paulo and has approximately 200,000 inhabitants, of whom ~37,000 are students ranging in age from 11 to 17 years old, distributed in 118 primary and secondary public  and private  schools.n = 1290 [73.6%]) and private schools (two schools: n = 462 [26.4%]). In each school, all of the students were invited to participate and received an informed written consent form, which was filled out by both the parents and the students before participating in the survey. The study was approved by the Ethics Committee on Human Experimentation of the Sao Paulo State University at Presidente Prudente.The sample size of 1495 subjects was estimated by means of an assumed PA prevalence of 41.8% ) between the two measures was high for both parents (k = 1.0) and adolescents (k = 0.85 [PA] and k = 0.87 [F-SES]).Potential confounder variables such as age, gender, level of parent education, and F-SES (according to the Brazilian Criterion for Economic Classification proposed by ANEP ) were al2) was used to evaluate the crude association between regular participation in sports and all leisure time behaviors. After the χ2 use, the Poisson regression with robust variance, represented by the prevalence ratio (PR) and 95% confidence interval (95%CI), was applied to indicate the possible effects of confounders . For the categorical variables, the agreement level was analyzed by the Kappa statistic. STATA 8.0  was used for all data management and all analyses were performed accounting for the sample design (svy set of commands available in STATA 8.0). The significance was set at 5%.Initially, the chi-squared test . Among the 448 students who refused participate, 198 were male and 205 female adolescents  and the mean age of this group was 13.1 (SD 1.5). Approximately 15% (n = 67) of the students who refused participate were enrolled in private schools. Among the 1752 adolescents analyzed, the response rate to both questionnaires was high .p = 0.002). Approximately 25% of the parents completed more than fourteen years of schooling and almost 30% of the sample was grouped into the highest F-SES. The prevalence of adolescents regularly engaged in sports was only 14.8%  and there was an association with gender .In Table The highest rate of L-frequency response (47.9%) was observed in the behavior 'walking' ('TV viewing': 8.6% and 'cycling': 46.1%), and the highest rate of H-frequency response (36.8%) was observed in the behavior 'TV viewing' .p = 0.142), however, it had an association with the frequency of cycling (p = 0.001). There was also an association among all the other active leisure time behaviors (data not shown).Of all analyzed leisure time behaviors, only the frequency of TV viewing was not associated with the frequency of walking  in comparison with those analyzed by Baumert et al.  who iden.8% in coFurthermore, there was an associated between male gender and higher engagement in sports, which concurs with other studies performed in both more and less developed settings ,7. RecenThe relationship observed between the regular participation in sports and all active behaviors confirms the first hypothesis of this study, since the positive and significant effect of the practice of sports on two active behaviors examined remained statistically significant after adjustment for important confounders associated with PA, such as gender and family socio-economic status. These findings are consistent with those of Baumert et al.  in whichLikewise, in a previous publication, Larson et al. , who anaMarshall et al.  in a metIn this present study, the results did not indicate that the regular participation in sports decreased TV viewing during leisure time, and for this reason, the secondary hypothesis of the present study was rejected.r = 0.01). Burke et al. [Although several important differences in the methods used in this study, such as the cross-sectional design and PA questionnaire use, must be considered for comparison of our results with previous data, this dissociation agrees with other studies from more developed nations. Ekelund et al.  among Eue et al. , among Ae et al.  in a lonThus, this lack of association seems to occur in both developed and developing countries. Future national surveys, principally in the context of developing nations, should analyze physical activity and inactivity as independent entities and not as the same variable anymore. Besides this, the implications of these results for public health policies are that the newer PA-promotion strategies should not only increase PAL, but also create separate strategies for decreasing the time spent on sedentary behaviors. Another implication is that in clinical practice, health professionals must take sedentary behaviors into account as important risk factors which are not beneficially influenced by PA and, hence, must create tools for combating these behaviors among pediatrics populations.In conclusion, this study presented data indicating that the regular participation in sports during adolescence is positively associated with higher frequencies of other active behaviors during leisure time. Furthermore, there was dissociation between regular sports practice and frequency of TV viewing, indicating that the results did not support the hypothesis that engagement in sports decreases the time spent on TV viewing during leisure time.PA: physical activity; PAL: physical activity level; L-Frequency: low frequency; M-Frequency: mid frequency; H-Frequency: high frequency; PR: prevalence ratio; 95% CI: confidence interval of 95%.The authors declare that they have no competing interests.RAF was the principal researcher responsible for the collection, analysis and interpretation of data, as well as for drafting the manuscript. JRC was involved in analysis and interpretation of data and also in critical revision of the paper. IFFJ,  ERVR, MRL and AROwere involved in revising the manuscript critically for important intellectual content.The pre-publication history for this paper can be accessed here:


Cardiac arrest (CA) is an indication for defibrillator (ICD) implantation unless it occurs in the context of an acute myocardial infarction (AMI). We investigated the ventricular arrhythmia (VA)-free survival of patients resuscitated from CA in the setting of AMI.We reviewed a database of 1600 AMI and CA survivors from which 48 patients were identified as having concurrent CA and AMI (CA+AMI group). Those patients were matched by age, gender, race, and left ventricular ejection fraction (LVEF) to 96 patients with AMI but no CA (AMI group) and 48 patients with CA but no AMI (CA group).Patients and controls were followed for 3.9±3.2 years. Patients in the 3 groups had similar baseline characteristics . The 5-year VA-free survival was 67%, 92%, and 80% for the CA+AMI, AMI, and CA groups, respectively, p<0.001.Patients with concurrent CA and AMI are at high risk of recurrent VA, with VA-free survival rates significantly worse than those of patients with AMI but no CA, and comparable to those of patients with CA outside the context of an AMI. Accordingly, these patients should be considered for ICD implantation. Patients with concurrent CA and AMI were found to be at high risk of recurrent VA, with VA-free survival rates significantly worse than those of patients with AMI but no CA, and comparable to those with CA only. Accordingly, these patients should be considered for ICD implantation. Cardiac arrest (CA) or hemodynamically compromising ventricular arrhythmias (VA) constitute an indication for defibrillator (ICD) implantation -3 exceptData from the AVID registry  suggest All patients who were admitted to the University of Pittsburgh Medical Center with CA concurrent with AMI between 1992 and 2000 were included in this study. Patients electronic medical records were analyzed for baseline demographics, electrocardiographic data, clinical characteristics, left ventricular ejection fraction (LVEF), laboratory data both upon admission and discharge, admission and peak cardiac enzymes, inpatient medications and therapies, discharge medication, echocardiographic data, left and right heart catheterization data, ICD implantation and therapies, and associated medical conditions.A total of 1600 records were reviewed, of which 48 consecutive patients with concurrent CA and AMI were identified. For each such patient, two controls with AMI but no CA and one with CA outside of the context of an AMI were identified and matched by age, gender, race and LVEF. A total of 192 patients were included in the analysis. All-cause mortality was obtained by reviewing medical records and by searching the National Social Security Death Index . The priContinuous variables were expressed as mean ± standard deviation and were compared using the student t-test. Categorical variables were compared using the Chi-square test. Times to event curves during the follow-up period were calculated by the Kaplan-Meier method and compared between groups using the log-rank tests. Multivariate analysis of the independent predictors of VA-free survival was performed using the Cox Proportional Hazards model. A two-tailed p-value of <0.05 was considered significant. All analyses were performed using SPSS 14.0 version .A total of 48 consecutive patients were admitted to the University of Pittsburgh Medical Center with concurrent CA and AMI. They were matched to 96 control patients with AMI but no CA and to 48 control patients with CA outside the context of an AMI. Cases and controls were followed at our institution for a mean duration of 3.9±3.2 years. The demographic and clinical characteristics of patients and controls are shown in Compared to the patients in the AMI group, patients in the CA+AMI group were more likely to have a history of coronary artery disease , of CA , and atrial fibrillation . Compared to patients in the CA group, cases (CA+AMI group) were less likely to have a history of cardiomyopathy . Also, the use of β-blockers, Angiotensin converting enzyme inhibitors, and anti-arrhythmic medications were higher in the survivors of concurrent CA and AMI compared to the patients in the control groups.As expected based on published guidelines , there wAt the time of admission to the hospital, there was evidence on the surface electrocardiogram of ST segment elevation AMI in 16 of 48 (33.3%) patients in the concurrent CA+AMI group compared to 52 of 96 (54.2%) in the AMI group (p=0.014). Of the 144 patients in the CA+AMI and AMI groups, 33 (16%) underwent revascularization (12 by percutaneous coronary intervention and 11 by coronary artery bypass grafting) at the time of the index hospitalization or during follow-up.We compared the time to death or first VA in the 3 patient study groups. Patients in the CA+AMI group had lower VA-free survival compared to patients in the control groups . Kaplan Meier curves were constructed to reflect the VA-free survival over the mean follow-up period of 3.9±3.2 years and are shown in The VA-free survival was analyzed in a multivariate Cox Regression model adjusting for such covariates as age, LVEF, QRS width, cardiac rhythm documented at the time of hospital admission, and implementation of therapies such as coronary revascularization, use of β-blockers, use of anti-arrhythmic drugs, and defibrillator implantation. After adjusting for all these covariates, patients with concurrent CA and AMI remained at a higher risk compared to the 2 control groups for death or recurrent VA .Patients with concurrent CA and AMI also had a higher incidence of VA when compared to patients with CA without AMI and patients with AMI without CA. The incidence of VA recurrence over the follow-up period was 57%, 40% and 11% in the CA+AMI, CA, and AMI groups, respectively (p<0.001). The incidence of VA among the 3 study groups is shown in The risk of VA was also analyzed using a multivariate binary logistic regression model. After correcting for age, LVEF, QRS width, cardiac rhythm documented at hospital admission, coronary revascularization, utilization of β-blockers, anti-arrhythmic drugs, and ICD implantation, patients with concurrent CA and AMI remained at a higher risk for VA recurrence .We analyzed the time to death in the 3 study groups. In the overall cohort, there was no difference in survival p=0.75, . BecauseOur data demonstrate that patients with concurrent CA and AMI are at significantly increased risk of death or recurrent VA compared to patients with AMI and no associated CA. Also, their risk exceeds that of patients with CA outside the immediate context of an AMI, a population that has an established indication for ICD implantation according to current published guidelines4 which are based on a number of large, randomized, prospective trials -3. This While current guidelines support the implantation of an ICD for patients with cardiomyopathy on the basis of persistently depressed left ventricular function and even in the absence of previous arrhythmic events ,9, surviSome studies  have queMechanistically, denying a life-saving therapy such as the ICD to patients with reversible causes of VA or CA is flawed for 2 reasons. First, patients who suffer a CA secondary to presumed reversible causes such as ischemia, myocardial injury, or electrolyte imbalances are at continued risk of recurring episodes of such reversible, albeit not avoidable, events. Second, The CA that happens secondary to a reversible cause may just reflect an underlying predisposition, genetic or other, in the survivor of such event i.e. a different trigger in the same subject may lead to a future CA because of a lower fibrillation threshold that the patient may have. Although speculative, these concerns are very plausible and have to be considered before denying a patient an ICD implantation because their CA was concurrent with an AMI.Our study has some limitations. First, the data was collected retrospectively and therefore its accuracy depends on the accuracy of the electronic medical records and clinical charts. Some patients who are not currently followed at our institution might have had VA after they were lost to follow-up, which could not be accounted for. In addition, patient compliance with standard medical therapy after hospital discharge could not be ascertained. Second, our study was a single center study with a moderate number of patients who were mainly male Caucasians. Extrapolating our results to other patient populations from different ethnic or geographic backgrounds may not be attainable.In summary, our data suggests that survivors of concurrent CA and AMI are at high risk for death and recurrent VA. While in the current guidelines these patients are denied ICD implantation, our study suggests that they may benefit from this life-saving therapy. Further prospective, randomized studies are however needed to establish the potential effect of the ICD on the overall mortality of survivors of concurrent CA and AMI before the current guidelines may be revised.


To the Editor: Kurth et al  who had been scratched by a cat with multiple cutaneous ulcerated lesions sought care at a local hospital; he had a lesion on his right hand, moderate fever, and malaise. Histopathologic findings from the cat indicated feline poxvirus infection. In July 2007, a female veterinarian (patient B) who lived in a different area of the same region and also had been scratched by a cat, sought care at the same hospital; she had a lesion close to the right sternoclavicular joint.On the basis of patients’ history of exposure and clinical presentation of the animals’ disease, zoonotic transmission of OPV infection was suspected. Vesicle fluid and, subsequently, crusts from the patients’ lesions, were sent to the virology laboratory of the reference center for poxvirus infections at National Institute for Infectious Diseases in Rome, where OPV diagnosis was based on electron microscopy, virus isolation, and detection of viral nucleic acid. In addition, serial blood samples were sent to the same laboratory for analysis of specific antibodies and cellular immune response.crmB gene (EF612710 and FJ445748) and on the complete sequence of the hemagglutinin gene (EF612709 and FJ445747). The hemagglutinin (crmB (not shown) sequences from each isolate formed a distinct cluster within the OPV genus; similar results were obtained from concatenated analysis of both genes (not shown). The identity/similarity scores of the complete nucleotide sequences of crmB and hemagglutinin genes from patient A, in relation to other OPVs, were, respectively, Ectromelia (AF012825), 0.598 and 0.841; cowpox (X94355), 0.933 and 0.927; vaccinia (AY678276), 0.844 and 0.934; camelpox (AY009086), 0.941 and 0.940; monkeypox (DQ011153), 0.909 and 0.914; and variola (DQ437588), 0.922 and 0.906. On the basis of these results, species assignment of the isolated OPVs was not possible. Preliminary sequence data on additional genes  from patient A’s isolate supported the segregation of these OPVs in Italy from the other known OPV species. However, the available information is still not enough to infer whether the isolates from Italy belong to a novel or known OPV species. More extensive biologic and molecular characterization is in progress.The viruses were almost identical, according to the partial sequence of the glutinin  and the The 2 cases reported here, occurring >1 year apart, indicate that OPV is circulating in domestic, and possibly wild, local fauna; they underscore the need for physicians and veterinarians to become aware of the risk for OPV zoonoses. A surveillance program has been launched among local veterinary clinics to identify nonvaccinated veterinarians who have been exposed to OPV. A surveillance plan for cats at these clinics has also been started.


Although laparoscopic surgery has been available for a long time and laparoscopic cholecystectomy has been performed universally, it is still not clear whether open appendectomy (OA) or laparoscopic appendectomy (LA) is the most appropriate surgical approach to acute appendicitis. The purpose of this work is to compare the therapeutic effects and safety of laparoscopic and conventional "open" appendectomy by means of a meta-analysis.A meta-analysis was performed of all randomized controlled trials published in English that compared LA and OA in adults and children between 1990 and 2009. Calculations were made of the effect sizes of: operating time, postoperative length of hospital stay, postoperative pain, return to normal activity, resumption of diet, complications rates, and conversion to open surgery. The effect sizes were then pooled by a fixed or random-effects model.Forty-four randomized controlled trials with 5292 patients were included in the meta-analysis. Operating time was 12.35 min longer for LA . Hospital stay after LA was 0.60 days shorter . Patients returned to their normal activity 4.52 days earlier after LA , and resumed their diet 0.34 days earlier. Pain after LA on the first postoperative day was significantly less (p = 0.008). The overall conversion rate from LA to OA was 9.51%. With regard to the rate of complications, wound infection after LA was definitely reduced , while postoperative ileus was not significantly reduced. However, intra-abdominal abscess (IAA), intraoperative bleeding and urinary tract infection (UIT) after LA, occurred slightly more frequently.LA provides considerable benefits over OA, including a shorter length of hospital stay, less postoperative pain, earlier postoperative recovery, and a lower complication rate. Furthermore, over the study period it was obvious that there had been a trend toward fewer differences in operating time for the two procedures. Although LA was associated with a slight increase in the incidence of IAA, intraoperative bleeding and UIT, it is a safe procedure. It may be that the widespread use of LA is due to its better therapeutic effect. Acute appendicitis is a common indication for abdominal surgery with a life-time incidence between 7 and 9% , and appConsidering research published in English, to date there have been some prospective randomized controlled studies comparing LA and OA. While some studies concluded that LA was superior to OA in terms of a faster recovery, improved wound healing, and earlier resumption of diet, other studies found no such benefits, or even favored conventional appendectomy. However, most of these studies had small sample sizes, and therefore the risk of a type II error (failing to observe a difference when in truth there is one) may be high. The statistical power of analysis can be increased through a meta-analysis, which combines and compares the data from different studies. The most recent meta-analysis of the two techniques was published 3 years ago , and manWe searched electronic databases  for potentially relevant randomized controlled trials comparing LA and OA conducted from January 1990 to December 2009, published in English. Keywords used for the search included: randomized controlled trial and appendectomy/appendicectomy, laparoscopic appendectomy/appendicectomy, laparoscopic versus open appendectomy/appendicectomy, minimally invasive versus conventional appendicectomy/appendectomy, and laparoscopic and open appendectomy/appendicectomy. The "related articles" function was used to broaden the search, and reference lists of these studies were reviewed to determine whether any other trials were potentially eligible for inclusion in the meta-analysis. Additionally, the abstracts from main international meetings  for the last 5 years were searched by manual retrieval, and the authors were asked to provide full information on their study using a detailed data extraction form. Two investigators independently reviewed all studies. Eligible trials were then selected according to the inclusion criteria below. Discrepancies were resolved, if necessary, by discussion and consulting a senior reviewer.We systematically reviewed each study according to the following criteria: (1) a prospective randomized study format only; (2) a comparison of laparoscopic and open appendicectomy; (3) The study reported at least one of the desirable outcomes mentioned below and the standard deviation of the mean for continuous outcomes of interest was reported or can be calculated; (4) Studies that allocated patients depending on the availability of staff or instruments were excluded; (5) Studies that used variations on the standard laparoscopic technique, including hybrid procedures or single trochar techniques, were also excluded.The outcomes of interest included operating time, postoperative length of hospital stay, resumption time of normal activities and diet, and postoperative pain  graded from 0 to 10, with 0 being no pain and 10 being the most intense pain). We were also interested in several complications including: wound infection, postoperative ileus, intraoperative bleeding (>500 mL), urinary tract infection (UTI) and intra-abdominal abscess (IAA) formation following LA vs. OA techniques.Two investigators independently extracted the following data from each included study: first author, country, year of publication, number of participants allocated to each intervention group, study population characteristics, severity of appendicitis, the desirable outcomes, the method of randomization and allocation concealment, the blinding of outcome assessment, conversion rate from LA to OA, and whether intention-to-treat analysis was used. Any disagreement was discussed and resolved by consensus. The Jadad scale  was usedMeta-analysis was performed using Cochrane Collaboration Review Manager 5.0 software. For continuous variables, statistical analysis was carried out using the weighted mean difference (WMD) as the summary statistic, comparing the treatment (LA) group with the reference (OA) group using the inverse variance method. A negative WMD favored the LA group, and the point estimate of the WMD was considered statistically significant at the p < 0.05 level if the 95% confidence interval (CI) did not include the value zero. For categorical variables, statistical analysis was carried out using the odds ratio (OR) as the summary statistic. An OR of less than one favored the LA group, and the point estimate of the OR was considered statistically significant at the p < 0.05 level if the 95% CI did not include the value one.2 which describes the proportion of total variation in study estimates that is due to heterogeneity. If the test rejects the assumption of homogeneity of studies, then it is not appropriate to use a fixed effects model [Fixed effects models were initially calculated for all outcomes. We then tested for homogeneity among the studies by calculating the Its model , and ranIf studies reported their continuous variables as medians with ranges that a meta-analysis can not use, we assumed that the mean is equal to the median value itself and estimated the standard deviation (SD) as a quarter of the range (samples ≤ 70) or range/6 (samples > 70) . If neitTo ensure finding the exact change in comparative outcomes between OA and LA, and because the LA procedure is relatively recent and experience with it has increased rapidly, the studies published before the year 2000 were analyzed separately from those published afterward.The search strategy generated 586 studies. After the initial screening, 51 studies were thought to meet the inclusion criteria -59. AfteAdditional file Thirty-six studies reported data that allowed quantitative pooled analysis for operating time  incidence of wound infection for LA, compared with 8.41% (174/2069) for OA. The difference was statistically significant  for OA, and 1.78% (28/1576) for LA. The effect size of the difference in the ORs, analyzed by a fixed effects model, was 0.91 . The meta-analysis with a fixed effects model suggested that the conventional approach led to a reduced incidence of intraoperative bleeding, however, the difference was not statistically significant  for OA and 1.75% (7/401) for LA. The effect size of the difference in ORs, analyzed by the fixed effects model, was 1.76  was not adopted or unclear, or included only males or females or children, or reported no measure of the standard deviation. Then heterogeneity was decreased. As shown in Additional file Concerning rates of complications, the possibility of publication bias was analyzed by the inverted funnel plot. The plot resembles a symmetric inverted funnel (the 95% CI). It is notable that in Figure Laparoscopy, as a minimally invasive technique, has unique advantages in several areas, and many scholars have tried to prove these advantages. Yet, because OA involves a small incision and perfect skill, the advantages of LA over OA continues to be debated. In order to confirm the greater efficacy of LA, we performed the present research. Compared to other meta-analyses -62, our'Regarding operating time, there was an obvious trend toward parity between the two procedures. A reputation for extended operating time is a major disadvantage, and has considerably influenced the widespread use of LA: according to an initial study, LA involved a significant increase in operating time . This maAccording to the analysis for the entire study period (1990-2009), the length of hospital stay after surgery was shortened in LA by 0.60 days, a difference that is not of clinical significance. However, since the year 2000 the reduction in postoperative hospital stay became more significant. A 48-hour discharge policy for LA proposed by Grewal et al.  contribuEarly return to full activity is accepted as an obvious advantage of LA, which was supported by a large scale meta-analysis conducted by the Cochrane Colorectal Cancer Group . The troPostoperative pain can be assessed quantitatively by the daily requirements for analgesics. Nevertheless, the various kinds of analgesics and routes of administration make it difficult to estimate pain relief. We qualitatively assessed pain on the first postoperative day by means of a VAS. The meta-analysis indicated that LA offered significant advantages in relieving postoperative pain (p = 0.008), mainly due to its minimal invasiveness. However, the difference in VAS between the two procedures was not statistically significant for the post-2000 subgroup of studies (p = 0.82). The trend toward a smaller incision in OA may explain this decreased difference.The reduction of wound infection is a significant advantage of LA. The chance of wound infection is greater in OA partly because the inflamed appendix is removed from the abdominal cavity directly through the wound, whereas in LA it is extracted via a bag or trocar. In addition, the port-site wounds in LA are smaller compared to the longer wounds of OA, especially in obese patients.There were several explanations for the reduction of ileus following LA. Firstly, decreased handling of the bowel during the procedure leads to less postoperative adhesion, and such adhesion may be responsible for ileus. Secondly, patients after LA had less opiate analgesics, which inhibited bowel movements in the postoperative period. Lastly, earlier mobilization after LA may also contribute to the reduction of adhesion.The finding that the incidence of IAA, intraoperative bleeding and UTI after LA was higher compared with OA should be noteworthy, even though these were not statistically significant. Intraoperative bleeding and UTI were rare complications after appendectomy. The reason why the rates were higher after LA is not clear, and the further investigation is necessary. IAA is a serious complication following appendectomy and can potentially be life threatening; many investigators pay close attention to this complication. Gupta et al.  considerIt is hard to understand why the conversion rate from LA to OA increased over time. Perhaps as experience with the laparoscopic procedure is gained, surgeons might attempt to perform LA for complicated cases such as gangrenous and perforated appendicitis, most of which might have been treated previously by the open approach. The increased difficulty in LA might have resulted in the higher conversion rate.Meta-analysis is an increasingly popular method of data analysis to solve debatable problems. However, there were some drawbacks in our research. First, different studies included in our research may have had slightly different defining criteria for the outcome measures, e.g., wound infection and ileus. Resumption of normal activity and diet might also be defined differently. Second, not all the studies measured data based on a double-blind. In the absence of a double-blind, subjective variables such as pain assessment could be considerably influenced by the enthusiasm for a novel technique. Third, there was variation in surgical techniques and treatment protocols amongst the studies, and therefore heterogeneity in the studies might exist. Fourth, although most studies were comparable with regard to age and sex, fewer were matched for severity of appendicitis  and weight. These considerations may have an influence on postoperative complications, recovery and operation time.Despite the limitations mentioned above, we believe that LA involves a shorter hospital stay, less postoperative pain, a faster recovery, and a lower complication rate compared with OA. Our study demonstrates that LA is a safe and effective treatment alternative for patients with acute appendicitis, and is recommended for those hospitals where laparoscopic expertise and equipment are available. Although LA was associated with slightly more operating time than OA, subgroup analysis revealed that this difference has been diminishing. The slightly higher incidence of IAA, intraoperative bleeding and UTI was worrisome, and due to insufficient primary data our research unfortunately was unable to stratify the postoperative abscess rate according to the severity of the appendicitis. Therefore, bias between groups might be present and might have affected the results. Further studies should match for the severity of appendicitis to settle the question.In conclusion, the present study shows that LA provides considerable benefits over OA, including a shorter hospital stay, less postoperative pain, earlier postoperative recovery, and lower complication rate. Therefore, the widespread use of LA is routinely recommended in those hospitals where laparoscopic expertise and equipment are available.The authors declare that they have no competing interests.XHL: collected, analyzed, interpreted data, wrote the manuscript. JLZ: planned, designed and corrected the manuscript. LXS: analyzed, interpreted data, and helped to draft the manuscript. WLZ: provided general advice, analyzed and interpreted data. ZQC: provided general advice, analyzed and interpreted data. XL: interpreted data, helped to correct the manuscript. YFL: participated in study design and revising the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/10/129/prepub4 tables. This additional file includes 4 large tables with the format of Microsoft Word. The titles of dataset are listed below: Table S1: Characteristics of 44 studies included in our meta-analysis. Table S2: Methodological quality of studies included in our meta-analysis. Table S3: Meta-analysis of different outcomes in all studies and in selective studies. Table S4: Meta-analysis of the complications in all studiesClick here for file


The Glasgow area has elevated levels of deprivation and is known for its poor health and associated negative health-related behaviours, which are socially patterned. Of interest is whether high smoking rates are explained by the area's socio-economic profile.Data on age, sex, current/previous smoking status, area deprivation, social class, education, economic activity, postcode sector, and health board region were available from Scottish Health Surveys conducted in 1995, 1998 and 2003. Multilevel logistic regression models were applied by sex, unadjusted and adjusted for age, survey year, and socio-economic factors, accounting for geographical hierarchy and missing data.Compared with the rest of Scotland, men living in Greater Glasgow were 30% and women 43% more likely to smoke  before adjustment. In adjusted results, the association between living in Greater Glasgow and current smoking was attenuated . Accounting for individuals who had been told to give up smoking by a medical person/excluding ex-smokers did not alter results.High levels of smoking in Greater Glasgow were attributable to its poorer socio-economic position and the strong social patterning of smoking. Tackling Glasgow's, and indeed Scotland's, poor health must involve policies to alleviate problems associated with poverty. Smoking is the major preventable cause of death and disability in the developed world. It is known to impact negatively on the risk of heart disease, stroke and cancer, especially of the lung. Lung canPatterns of ill-health that characterise the Glasgow area may be due to some unknown 'Glasgow effect' adversely affecting the city's health beyond that explained by conventional risk factors. The extent to which elevated levels of smoking in Glasgow can be accounted for by socio-economic differences, or are truly attributable to a separate 'Glasgow effect', has not been addressed.Since smoking patterns vary with age and sex as well as over time,  investigSince individuals with smoking-related health problems may have stopped smoking on medical advice,  and therThe aim of this paper is to investigate whether differences in smoking status between adults living in the Glasgow area and the rest of Scotland can be explained by socio-economic factors, taking into account the additional effects of context and prior smoking status – considered both in terms of receipt of medical advice to stop smoking and by excluding those who stopped following medical advice.Data are from three cross-sectional Scottish Health Surveys in which nationally representative samples of the population living in private households in Scotland were interviewed in person in 1995,  1998 2121 and 20e.g. doctor or nurse) ever advised you to stop smoking altogether because of your health?" "Yes" or "No"). Information on postcode sector, health board region and socio-economic factors were also available.Smoking status was established by firstly asking respondents whether they had ever smoked a cigarette, a cigar or a pipe . If they answered "Yes", they were then asked if they currently smoke cigarettes   RespondeFour socio-economic measures were compatible for all three surveys: the 1991 area based Carstairs index of material deprivation,  occupati2 and χ2 for trend tests. Multilevel logistic regression analyses were performed by sex, unadjusted and adjusted for age and survey year, and socio-economic factors, accounting for the hierarchy of individuals within postcode sector areas. The impact of the differential socio-economic profiles between Greater Glasgow and the rest of Scotland was examined by comparing unadjusted and adjusted odds ratio (OR) estimates. To avoid survey non-response bias, differential weighting combined postcode sector, household and individual probabilities as well as ensuring the weighted sample matched population estimates for age, sex and health boards. Any difference in the relationship between cigarette smoking and Greater Glasgow residence for different survey years was assessed by the joint χ2 testing of the significance of interaction terms in the model. Accounting for individuals advised by a medical person to stop smoking was done in two ways: adjustment was made for anyone advised to stop smoking, and separately, ex-smokers who stopped following advice were excluded from analyses. Since only the age range 16–64 years were common to all three surveys, sensitivity analyses were conducted restricting the sample to these core age groups to check consistency.Differences in socio-demographic characteristics between Greater Glasgow and the rest of Scotland, and in socio-demographic characteristics by smoking status were assessed by χMissing smoking status, social class, education, and economic activity data were multiply imputed using the chained equations procedure,  with 5 iAnalyses were conducted using MLwiN 2.02 and STATA 9.1 statistical software packages.p =< 0.001); most markedly Greater Glasgow had far larger numbers living in the most deprived Carstairs quintile areas (p =< 0.001). However, the social class distribution in Greater Glasgow was no different to that of the rest of Scotland (p = 0.204). Compared with the rest of Scotland, Greater Glasgow residence was positively associated with the extent of missingness for social class, economic activity and education.For 1995, 1998 and 2003 surveys combined, 11,075 (44.1%) men and 14,052 (55.9%) women participated. Of all respondents, smoking status was collected for 11,033 (99.6%) men and 14,003 (99.6%) women (Table p < 0.001) (Table p < 0.001 for both men and women). Prevalence was significantly associated with deprived area of residence, low social class, unemployment/economic inactivity and low educational attainment . Although smoking status was not significantly different in men with known and unknown social class (p = 0.459), economic activity (p = 0.428), or education (p = 0.887), nor in women with known and unknown education (p = 0.081), it was significantly higher in women with unknown compared with known social class (p < 0.001) and economic activity (p = 0.006).For the whole of Scotland 33% of both men and women were current smokers, whereas prevalence for Greater Glasgow was 38% of men and 40% of women, significantly higher than the 32% for both men and women in the rest of the country (χ2(2 degrees of freedom (df)) = 2.167, p = 0.338 for men; χ2 (2 df) = 1.726; p = 0.422 for women), it was valid to perform all analyses on combined data from all three survey years. Univariably, compared with the rest of Scotland, men living in Greater Glasgow were 30% more likely to smoke: odds ratio (OR) = 1.30, (95% CI = 1.08–1.56) and women 43% more likely  . It may be that among smokers, cigarette consumption is higher in Glasgow than the rest of the country. It is known, for instance, that nicotine intake among smokers is higher in lower socio-economic groups, [There were a number of limitations to the survey data used for this study which should be acknowledged. Smoking status in the Scottish Health Survey is ascertained by self-report which is known to underestimate true prevalence . Althoug groups,  and that groups,  this may groups,  However, groups,  and so tStrengths of this study include breadth of socio-economic indicators, representativeness and the large sample size. Since a broad range of measures – covering area deprivation, household social class, individual economic activity and education attainment – was used, a comprehensive socio-economic profile has been captured, minimizing problems with measurement inadequacies. Analyses are based on rigorously collected data on over 25,000 individuals, characteristic of the general population, for whom smoking status was reported in all but a small number of cases. Finally, the additional analyses conducted accounting for medical advice to stop smoking and excluding ex-smokers provide robust evidence to support the findings that socio-economic circumstances explain elevated smoking levels in the Glasgow area compared with the rest of Scotland. There were higher levels of missing social class, economic activity and education data in Greater Glasgow, and smoking status was significantly higher in women with unknown social class and economic activity, underlining the need for sensitivity analyses based on multiply imputed data. Contrary to the tabulated complete case analyses results, those based on imputed data remained borderline significant for women, indicating some bias in the incomplete cases. However, overall, analyses based on imputed data confirmed attenuation in both men and women.In summary, individual and area socio-economic circumstances drive elevated smoking levels in the Glasgow area compared with the rest of Scotland, especially among men, reflecting its poorer socio-economic position. Within socially homogenous groups, smoking rates were similar in Greater Glasgow compared with the rest of the country.Since the strong social patterning of cigarette smoking in Greater Glasgow is equivalent to that seen elsewhere in Scotland, addressing the poor health of the population – at least in terms of smoking-related diseases – extends beyond Glasgow to national requirements to address the high levels of smoking (and the causes of smoking) among the most disadvantaged social groups. Thus tackling smoking-related health problems requires policies to address poverty, not just in Greater Glasgow but in Scotland as a whole. Future research could investigate to what extent higher smoking rates and other health risk behaviours explain high morbidity and mortality in the Glasgow area, and the degree to which associations are mediated by deprivation.The authors declare that they have no competing interests.Formulation of the research question arose from discussion between both authors. Analyses were planned and performed, and the draft of the manuscript was prepared by LG. AL contributed to the writing of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: