Dietary pattern may influence the risks of cardiovascular disease, atherosclerosis, type 2 diabetes, and metabolic syndrome through its effects on inflammation. We evaluated the association between dietary pattern and serum high-sensitivity C-reactive protein (hs-CRP) in a Japanese population.In this cross-sectional analysis, we used baseline data from 3905 men and 5640 women (age 40–69 years) who participated in a population-based cohort study between November 2005 and December 2007. Participants with possible inflammation-related diseases, current analgesic use, high hs-CRP levels (≥3000 ng/mL) or extreme dietary energy intake were excluded. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis.P-trend: 0.01, 0.06, and <0.01, respectively) and positively associated with the seafood pattern (P-trend = 0.02). In women, hs-CRP levels were inversely associated with the healthy pattern (P-trend = 0.06) and positively associated with the Western pattern (P-trend = 0.06).We identified 5 dietary patterns: healthy (high in vegetables and fruit), Western (high in meat and fried foods), seafood , bread (high in bread and low in rice), and dessert (high in confections and fruit). After adjustment for age, alcohol use, smoking, physical activity, and body mass index, hs-CRP levels in men were inversely associated with the healthy, bread, and dessert patterns  require further study. It is secreted primarily by the liver after its synthesis is triggered by pro-inflammatory cytokines such as interleukin-6, which is thought to be released by adipose tissue.2 Current evidence suggests that elevated blood levels of CRP are associated with older age, obesity, smoking, no or heavy alcohol intake, and a lower level of physical activity.6–10 Intakes of some nutrients or foods  have also been reported to be associated with serum CRP concentration.11–14Chronic inflammation is independently and directly associated with cardiovascular disease, atherosclerosis, type 2 diabetes, and metabolic syndrome.15,16 Accordingly, dietary pattern analysis, which examines the effects of overall diet, has emerged as an alternative and complementary approach. The association between dietary patterns and serum CRP has been explored in several studies,17–22 but the results have been inconsistent.People typically consume meals consisting of a variety of foods, with complex combinations of nutrients, rather than isolated nutrients. The traditional approach of studying single nutrients or foods may therefore be limited in terms of 1) possible interactions and high intercorrelations between various food components, which may make it difficult to evaluate the overall or independent effects of different nutrients or foods, 2) possibly small and thus undetectable effects of a single nutrient, and 3) the issue of multiple comparison.18,20,21 but not in others.17,19,22 In addition, several studies have demonstrated that a Western, or high fat and processed meat, pattern  is related to elevated serum CRP,17–20 although some studies did not corroborate this finding.21,22 To our knowledge, there has been only 1 cross-sectional study of dietary patterns and CRP in Japan. In that study, a healthy dietary pattern was strongly associated with lower serum CRP, and a seafood pattern was possibly related to higher CRP.21 The objective of the present study was to evaluate more comprehensively the association between dietary pattern and serum CRP in a Japanese population.An association between a healthy, or prudent, dietary pattern  and decreased levels of serum CRP has been reported in some studies,23 The subjects and methods of our cohort study (designated the Saga J-MICC Study) are described in detail elsewhere.24 Eligible subjects in the Saga study were all residents of the area corresponding to the former city of Saga (in the center of the current city of Saga) and were between the ages of 40 and 69 years at the time of the baseline survey for the Saga J-MICC Study. The former city of Saga was administratively consolidated with 4 adjacent municipalities on 1 October 2005. Candidates were enrolled by using the name, sex, date of birth, and address of all residents on the resident register in the city office. A total of 61 447 residents were invited by mail to participate in the baseline survey, which was administered between 1 November 2005 and 22 December 2007 in public halls and other available venues near the residential areas of participants. In total, 12 078 subjects  completed the baseline survey. Written informed consent was obtained from all participants, and the study protocol was approved by the Ethics Committees at both the Saga University Faculty of Medicine and the Nagoya University Graduate School of Medicine.In November 2005, we initiated a population-based prospective cohort study in Saga Prefecture, in northern Kyusyu island, as part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study), which aims to obtain fundamental data on the prevention and genetics of lifestyle-related diseases, particularly cancer.A self-administered questionnaire that included questions on alcohol consumption, smoking, and dietary habits, as well as current medication and past disease history, was sent to participants beforehand. They were instructed to bring their completed questionnaires to the survey location. On the day of the survey, a research nurse or nutritionist asked participants about any missing or inconsistent answers. Height and weight were measured to the nearest 0.1 cm and 0.1 kg, respectively. Venous blood was drawn from each participant, and serum, plasma, and buffy coat were separated within 3 hours and stored at −80°C until tested. Subjects were instructed to wear a single-axis accelerometer  on either side of the hip, except when sleeping or bathing, for 10 days after the baseline survey.sake, shochu (a Japanese distilled beverage), chuhai (shochu plus mixer), beer, whiskey, and wine. The categories of consumption frequency were: almost none, 1 to 3 days/month, 1 to 2 days/week, 3 to 4 days/week, 5 to 6 days/week, and daily, and the amount of each beverage consumed per day was reported. Total ethanol consumption per day for current drinkers was estimated based on beverage-specific ethanol concentrations. As for smoking habits, subjects were first asked about current smoking status (and cessation time for former smokers). Current and former smokers reported their usual cigarette consumption (cigarettes/day) and the age at which they started smoking. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m). Physical activity level (PAL) was calculated as total energy expenditure  divided by basal metabolic rate ; the former was estimated from the accelerometer as average daily energy expenditure , and the latter was defined as basal metabolism standard25 × body surface area26 × 24 hours. The calculation of energy expenditure by accelerometer has been validated in adults.27We assessed consumption of 6 types of alcoholic beverages: 28–31 This FFQ was designed to assess the average intakes of 47 of foods and beverage  items over the past year. A validation study comparing this FFQ and 3-day weighed diet records revealed that deattenuated, log-transformed, and energy-adjusted Pearson’s correlation coefficients for 26 nutrient intakes ranged from 0.12 to 0.86 (median: 0.45) in males, and from 0.10 to 0.66 (median: 0.38) in females, although mean daily nutrient intakes estimated using the FFQ were generally lower than those estimated from diet records.29 Because only 1 item was used to measure alcohol consumption in that FFQ,28 this question was removed, and the remaining 46 items were used in this study. Amounts and frequencies were ascertained for 3 staple foods  eaten at breakfast, lunch, and supper. The frequency categories (and daily frequencies assigned) for the staple foods were: almost none (0), 1 to 3 times/month (0.1), 1 to 2 times/week (0.2), 3 to 4 times/week (0.5), 5 to 6 times/week (0.8), and daily (1). Each staple food consumed at each meal was converted into bowls/day for rice and noodles or slices (or rolls)/day for bread, and the values obtained for 3 meals were summed. For the other 43 dietary items, only frequency options were given, as follows (assigned daily frequencies in parentheses): almost none (0), 1 to 3 times/month (0.1), 1 to 2 times/week (0.2), 3 to 4 times/week (0.5), 5 to 6 times/week (0.8), once/day (1), twice/day (2), and ≥3 times/day (3).Information on diet was collected using a validated short food frequency questionnaire (FFQ) developed by Tokudome et al.n = 212). Intra- and interassay coefficients of variation for the assay were 3.1% and 1.3%, respectively, at the laboratory.Parts of the stored serum specimens were sent to an external laboratory , and high-sensitivity CRP (hs-CRP) concentrations were measured using a latex-enhanced immunonephelometric assay on a BN II analyzer . The detection limit of this assay was 50 ng/mL, which was assigned to values below that limit (n = 53), 2) any history of possible inflammation-related disease , 3) current use of analgesics (n = 328), 4) hs-CRP concentration of 3000 ng/mL or higher (n = 592), and 5) dietary energy intake less than 500 or greater than or equal to 3500 kcal/day (n = 8). Consequently, 9545 subjects (3905 men and 5640 women) remained for analysis. Among these subjects, some were missing data on alcohol consumption (4 men and 5 women), smoking (1 man and 1 woman), BMI (4 men and 3 women), and PAL (58 men and 56 women).In the data analysis, we excluded subjects with any of the following conditions: 1) missing data on hs-CRP or dietary habits  of the daily amounts for 3 staple foods and daily frequencies for the other 43 items was performed by using the factor procedure of SAS. The identified factors were rotated by orthogonal transformation (varimax rotation) to improve their interpretability. The natural interpretation of the rotated factors in conjunction with eigenvalues larger than 1 (satisfied for 13 factors in men and 12 factors in women) and the scree plot  for the corresponding factors before their rotation determined whether a factor should be retained. Accordingly, we evaluated both 4- and 5-factor solutions for each sex, but the 5-factor solution after rotation yielded a more comparable interpretation between men and women. The derived factors (dietary patterns) were labeled based on our interpretation of the data, as well as on the relevant literature. The factor score for each dietary pattern (the dietary pattern score) in an individual was estimated as a linear combination of the standardized values for the food items and the standardized scoring coefficients.All analyses were performed separately for men and women with the SAS statistical software package . Selected major nutrient intakes were estimated by a SAS program utilizing the information from the FFQ and the standard tables of food composition in Japan (fifth revised edition).t test was used to analyze differences in means and the chi-square test was used to evaluate differences in proportions. The associations of each dietary pattern score  with selected characteristics at baseline were evaluated by linear regression analysis (for continuous variables) or the Mantel test . Adjusted geometric means of hs-CRP and their 95% confidence intervals by quintiles of each dietary pattern score were computed using the general linear model (GLM) procedure of SAS  in 3 different models, to control for potential confounding effects by other factors. The first model was adjusted for age (years) only. The second model was further adjusted for alcohol consumption , smoking , and PAL (continuous). In the third model, BMI was additionally controlled for. Since BMI may represent an intermediate step for possible associations between hs-CRP and dietary patterns, the second and third models were examined separately. The linear trend of the association between hs-CRP and each dietary pattern score was assessed by including in the model a continuous variable with the median value of the score within each quintile category, as well as covariates. A P value less than 0.05 was considered statistically significant.Because the distribution of hs-CRP concentrations was highly skewed to the right, the natural logarithm of hs-CRP was used in all analyses, and the resulting geometric means are presented. In univariate analyses, the 2), whereas women had a higher average PAL (1.458 versus 1.467). Men had higher intakes of total energy, carbohydrate, protein, and sodium, and lower intakes of fat, iron, vitamin C, and dietary fiber, than women. The geometric mean of hs-CRP for men was 422 ng/mL, which was significantly higher than that for women (299 ng/mL).Table The results from factor analysis of dietary patterns  are shown in Table Table P for trend <0.01). However, additional adjustment for BMI substantially attenuated this inverse association (P = 0.01 in men and P = 0.06 in women). After adjustment for all factors except BMI, the Western dietary pattern was significantly positively associated with hs-CRP only in women (P < 0.01), but the association was marginal (P =0.06) after further adjustment for BMI. The seafood pattern was significantly associated with elevated hs-CRP in men only (P = 0.02), even after full adjustment. The bread pattern was inversely associated with hs-CRP in men (P = 0.04) and women (P < 0.01), without adjusting for BMI; however, after adjustment for BMI, this association became marginal in men (P = 0.06) and nonsignificant in women (P = 0.33). The dessert pattern was strongly inversely associated with hs-CRP in men only, before and after adjustment for BMI (P < 0.01).The adjusted geometric means of serum hs-CRP and their 95% confidence intervals by quintiles of each dietary pattern score are shown in Table 17–21,33–35 Analysis of our findings revealed some similarities and some differences with those of previous reports. The healthy pattern  and Western pattern  identified in our study are analogous to similarly named patterns used in previous studies of other Japanese populations21,33–35 and Western populations.17–19 A pattern similar to the bread pattern in the current study was defined as a Westernized breakfast pattern in 2 previous Japanese studies.21,36 One of those studies also observed a seafood pattern similar to the pattern we noted.21 The dessert pattern observed in the present study has not been documented in previous studies. We speculate that this pattern might emerge if future studies derive 5 or more dietary patterns, especially in Japanese populations; however, it might be specific to our study population. Further study of this issue is necessary.In this study of a middle-aged Japanese population, we identified 5 major dietary patterns—healthy, Western, seafood, bread, and dessert—in both men and women. Most previous studies of diet reported 2 to 4 dietary patterns in 1 sex or both sexes combined.18,20,21 but not all,17,19,22 previous studies. High intakes of vegetables and fruit have consistently been used to characterize the healthy/prudent dietary pattern17,18,20,21 and have also been associated with lower serum CRP in several studies.13,37–39 The beneficial combinations of antioxidant vitamins38,39 and fiber12 contained in vegetables and fruit may partly mediate this inverse association between healthy dietary pattern and CRP. However, it was evident in our results that this inverse association was partly explained by the association between lower BMI and the healthy dietary pattern. We observed that, after additional adjustment for BMI, the resulting downward trend was not as steep as that reported previously in a Japanese population, particularly in women.21This study is one of the largest cross-sectional studies of the association between dietary patterns and CRP and further supports an inverse association between a healthy/prudent dietary pattern and hs-CRP, a finding that has been observed in some,17–19 and Iranian20 populations, but not in Japanese21 or Alaskan Eskimos.22 We observed a positive association between the Western pattern and hs-CRP only in women, and this association was largely mediated by increasing BMI. The Western pattern score was significantly positively associated with estimated fat intake (Table 19 and 27%–31% in Iranian women20). This may partially explain the absence, or weakening, of an association between hs-CRP and the Western dietary pattern in this study.The Western pattern, characterized by high intakes of red meat, refined grains, processed meat, and high-fat dairy products, has consistently been associated with higher CRP concentrations in Westernke Table , but fat14 and seafood-based long-chain n-3 PUFAs 40 are inversely associated with serum CRP concentrations, although these findings have not been consistent.11,41,42 In the current study, we unexpectedly found that the seafood pattern was positively associated with serum hs-CRP in men, even in the fully adjusted model. A Japanese study evaluated the relation between serum hs-CRP and a seafood dietary pattern , and trends toward positive associations were found (P for trend: 0.10 in men and 0.05 in women).21 In our male subjects, fish had a lower factor loading (0.40) in the seafood pattern than did other seafood such as shellfish (0.68), squid/octopus/shrimp/crab (0.64), and fish roe (0.46), and estimated intake of n-3 PUFAs was more strongly associated with the healthy or Western pattern than with the seafood pattern , however, we currently have no conclusive explanation for the above finding. The seafood dietary pattern in men was associated with elevated hs-CRP in current drinkers, but not in never or former drinkers (data not shown), and thus we cannot exclude the possibility of residual confounding by alcohol consumption. The factor loadings for the seafood pattern in women differed somewhat from those in men , which may partly account for the lack of a corresponding association in women.Several studies have reported that intakes of fishThe bread pattern in the present study can be viewed as the reverse of the traditional Japanese staple food pattern  and was significantly inversely associated with total energy intake as well as carbohydrate intake Table . The obs45 may have confounded those associations, although additional adjustment for hyperlipidemia medication status did not materially alter the current results (data not shown). Thus, our findings need to be confirmed, particularly within other Japanese populations, by well-designed studies that take full account of potential confounders.Some limitations of the present study must be considered. First, due to its cross-sectional design, reverse causation could potentially account for the observed associations. However, we excluded individuals with possible inflammation-related disease or high hs-CRP levels. In addition, most participants did not know their current hs-CRP status, which is not usually tested in health screenings and clinical situations. Because hs-CRP levels in the study subjects were mostly within the normal range, it appears unlikely that elevated or low hs-CRP levels caused a change in their dietary habits. Second, the participation rate of this study was relatively low (about 20%). If subjects with a certain hs-CRP level  who also possessed some dietary habit  were more likely to participate for some reason, this could have led to selection bias. However, this possibility also seems unlikely because most subjects were unaware of their hs-CRP status, as described above. Third, our factor analysis was limited in terms of subjectivity in determining and labeling dietary patterns and the difficulty in extrapolating the findings to other populations. Fourth, residual confounding by uncontrolled or unmeasured factors may have distorted true associations with the dietary patterns we identified, which were significantly associated with many important covariates, as shown in Table In conclusion, we identified 5 major dietary patterns in a Japanese population. Our results indicate that the healthy dietary pattern may be associated with suppressed inflammation, as reflected by decreased hs-CRP, independently of BMI and other factors, in both Japanese men and women. Additional studies are required to assess the possible sex-specific associations of hs-CRP with other dietary patterns .


Objective: Toxic epidermal necrolysis and Stevens-Johnson syndrome have related high morbidity and mortality. We predict that preexisting multimorbidity is a major prognostic factor of both these diseases. Methods: A retrospective analysis in toxic epidermal necrolysis and Stevens-Johnson syndrome patients over the past 10 years. Three severity categories  were defined according to a point-rating system. Results: Twenty-seven inpatients, with a median age of 63 years, diagnosed with toxic epidermal necrolysis (n = 13) or Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 14) were assessed in this study. Of these, 14 patients died during the course of the study. Nonsurvivors showed significantly higher multimorbidity (P = .038), with higher scoring on the points system for disease severity (P = .003), than survivors and CART (Classification and Regression Trees) cross-validation (P < .05). Limitations: Restricted number of patients due to low prevalence rate. Conclusion: The complexity of associated multimorbidity appears to have a large influence on toxic epidermal necrolysis and Stevens-Johnson syndrome prognosis, which has not been considered in any of the established scoring systems. Both diseases are associated with high morbidity and a mortality rate of approximately 85%. There is a high risk of super-infection and sepsis due to subepidermal and mucosal blisters, like superficial second-degree burn wounds. In addition to the initial diagnosis of SJS/TEN, patients often present with multiple morbidities (MMs), which may be important predictors of outcome. The use of multimorbidity is becoming increasingly more common to describe the co-occurrence of multiple chronic or acute diseases in a single patient, without reference to an index condition,1The study described herein was based on a 10-year retrospective analysis of the major influences of MM on prognosis.Twenty-seven patients with highly confirmed clinical and histopathological diagnosis of TEN or SJS were treated over a 10-year period. A clinical diagnosis was defined by the validated results of the Documentation Center for Severe Skin Reactions of the German Registry, Freiburg, which induced the leading RegiSCAR study. All patient data were analyzed retrospective to age, sex, necessity of ventilation, catecholamine administration, occurrence of skin reaction inside or outside the hospital, and outcome.Each individual prognosis was also calculated by the widely used TEN scoring system, SCORTEN, if sufficient data were available. Each of the 7 criteria receiving 1 point were as follows: (1) age more than 40 years, (2) malignancy, (3) tachycardia more than 120 per minute, (4) blistering more than 10% of total affected body surface area (TBSA), (5) urea serum more than 10 mmol/L, (6) bicarbonate less than 20 mmol/L, and (7) glucose serum more than 250 mg/dL.As multimorbidity has still not been considered in the scoring, we analyzed its impact on the prognosis of TEN/SJS patients. To this end, we decided to define 3 severity categories with a point rating system: (1) minor MMs—have no or trivial impact on outcome during hospitalization; (2) moderate MMs—have classical risk factors defined by the World Health Organisation; and (3) severe MMs—have life-threatening or life-shortening morbidities, increasing the likelihood of poor outcome with or without treatment. Postoperative immunodeficiency, malignancy, AIDS, and embolism are examples of MMs that are associated with TEN/SJS. As an assessment of the TBSA is prone to a subjective judgement of redness and bullae, this criterion was excluded.,Each potential risk was correlated with information obtained through guideline research . The 3 categories mentioned earlier were chosen, as we believe that MMs should be rated according to their severity. Hence, mild, moderate, or severe MMs receive 1, 2, or 3 points, respectively. Each patient was analyzed individually by the number and severity of MMs, and the risk was calculated by their total point scoring. For better illustration, all included diseases and their assignment are shown in Tables 3TEN n = 13), SJS (n = 1), or SJS/TEN overlap (n = 13) were confirmed histologically in 27 patients, as shown by the patient series in Table 3, SJS (nP = 0.197).With regard to age and outcome, survivors had a median of 59 years (IQR 6), whereas nonsurvivors had a median age of 67 years (IQR 33). Although the range of median age varied considerably, the IQR of the nonsurvivors showed a larger range than the survivors, as there was also morbidity among younger patients. A significant age-dependent mortality was not seen by the Mann-Whitney test for independent factors (P = 0.163), although the small number of each group could be a limitation in this result.When subdivided into gender and subgroups of SJS/TEN versus TEN, the distribution was almost equal in the SJS/TEN overlap , of which 5 female and 1 male patients died. Ten female and 3 male patients presented with a diagnosis of TEN, of which 6 female and 2 male patients died. There was no statistically significant difference in mortality between sexes .The time lapse between eventual first manifestation and admission to our intensive care ward was 0 to 39 days . No statistical significance could be seen in mortality by the Mann-Whitney No patients scored 1 point or less, with a survival prediction of 100%. In total, mortality was predicted as 35.3% or 77.8% in 10 patients (SCORTEN 4 and 5 points), of whom 4 survived, with 3 scoring 5 points. In contrast, mortality prediction of 13 patients was as low as 6.7% and 23.8% (SCORTEN 2 to 3 points), of whom approximately 50% died. In conclusion, prediction based on SCORTEN was accurate for only 55.56% patients.Our patient series showed a median of 4 MMs per patient (0-8 MMs) Table , with 63On the basis of the categorization as described earlier, our data showed on average 1.7 mild (median 1), 3.1 moderate (median 3), and 2.3 severe (median 2) MMs per person.When divided into 2 subgroups based on patient mortality, our data revealed that nonsurvivors had 2 to 8 MMs .During our study, 11 out of 14 nonsurvivors had 1 to 5 life-shortening MMs, 10 of whom had another moderate MM. Three nonsurvivors without any severe MM were aged between 77 and 88 years and suffered from 1 to 6 moderate MMs. Only one of the 17 survivors had a severe MM, with malignant media infarction. The survival group showed 0 to 6 MMs . One patient, without any chronic disease, had an infection of the urinary tract and received antibiotic trigger medication. Four surviving patients incurred minimal MMs, such as flue, conjunctivitis, or organic brain syndrome.The majority of MMs in the survival group were well-known risk factors, such as systemic cardiac , kidney and lung diseases, diabetes mellitus, and rheumatoid disorders.Figure U test for statistical analysis of independent variables, a significant difference could be seen in the number of MMs in survivors compared with nonsurvivors, with a higher incidence in nonsurvivors (P = 0.038). A highly significant difference could also be seen in the total score for each MM subgroup according to our scoring system (P = 0.003)   Fig . In the P value of 0.013, with the number of MMs also being significant .Concerning our question of whether preexisting cardiac diseases influence patient outcome, Fisher exact test had a P ≤ 0.0001; odds ratio 44; confidence interval: 3.966-488.188). With regard to the 2 groups defined by the CART analyses, all patients with more than 12 points total score, and who also died, required catecholamine application. A correlation between necessity for catecholamines and the total points of MM assigned by our categorization system was significant . However, only a tendency toward the total number of MMs could be reached . Statistical analysis showed a significant difference between the requirement for catecholamine application and subdivision of histopathological diagnoses .Catecholamine application was necessary in 12 cases, of which 11 died. Chi-square test revealed a high significance between the requirement of catecholamines and mortality 6,8,16,17There is a great need for a scoring system that incorporates potential predictors for prognosis and mortality of SJS and TEN.6-20-18,Bastuji-Garin et al developed a specific TEN scoring system (SCORTEN) that makes inter-individual prognoses in SJS/TEN patients18In our opinion, variations in biological tests  are affected by parameters such as time of blood sampling, state of vigilance, and pain during measurements. The 2 SCORTEN parameters incorporating age more than 40 years and TBSA (>10%), with or without inflicted mucosa, are very likely predictors, as can be seen in our cohort. Determining the affected TBSA requires experience in the examination and is still subjective, often leading to overestimations.-1,30-34-Furthermore, other groups are also critical of the SCORTEN method and believe that further assessments are needed for it to be more accurate.26In our opinion, chronic morbidities other than malignancies have to be critically discussed as having an influence on the outcome in TEN/SJS, for reasons described herein. On the basis of our new categorization system of multimorbidity subgroups, which considers their total number and intraindividual severity, we could significantly calculate patient prognosis.As expected, patients with a high number of severe MMs, which singularly harbor a higher risk of mortality, had a higher mortality rate than patients with moderate or mild MMs. None of the patients died with no or mild MM, even if they had to be ventilated for up to 52 days.Because of the low incidence of medication-associated serious exfoliative skin diseases, it is difficult to recruit an adequate number of patients to be representative. As shown by the Center of Quality and Management in Health Care, Medical Council Niedersachsen, the number of cases in our study is sufficient to show the impact of MM on the prognosis of medication-associated serious exfoliative skin diseases. However, a multicenter study may be more effective at obtaining a larger number of patients and more significant results.Current literature does not consider the complexity of preexisting MMs in the prognosis of TEN/SJS, even though they seem to have a great impact on patient outcome. We do not suggest that our scoring system should replace other well-established and well-tested existing morbidity scoring systems, but we do believe that multimorbidity, which appears to have a significant effect on outcome from our results, should be included in these scoring systems. Although the number of patients in our group was quite small, the influence of MM on the prognosis of clinical outcome was to be statistically significant.


Hypnotics are widely used by the elderly, and their impact on mortality remains controversial. The inconsistent findings could be due to methodological limitations, notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use, for example, insomnia symptoms and excessive daytime sleepiness, depression and anxiety. Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders and sleep complaints.Analyses were carried out on 6,696 participants aged 65 years or older randomly recruited from three French cities and free of dementia at baseline. Adjusted Cox proportional hazards models with delayed entry, and age of the participants as the time scale, were used to determine the association between hypnotic use and 12-year survival.At baseline, 21.7% of the participants regularly used at least one hypnotic. During follow-up, 1,307 persons died, 480 from cancer and 344 from cardiovascular disease. Analyses adjusted for study center, age and gender showed a significantly greater risk of all-cause and cardiovascular-related mortality with hypnotics, particularly benzodiazepines, and this increased with the number of hypnotics used. None of these associations were significant in models adjusting for sociodemographic and lifestyle characteristics, chronic disorders including cardiovascular pathologies, sleep and psychiatric disorders. Results remained unchanged when duration of past hypnotic intake or persistent versus intermittent use during follow-up were taken into account.When controlling for a large range of potential confounders, the risk of mortality was not significantly associated with hypnotic use regardless of the type and duration. Underlying psychiatric disorders appear to be the principal confounders of the observed association. Insomniper se-4. Insomper se,6 and psper se,4,7.Hypnotics are indicated for treating insomnia symptoms, including those associated with anxiety and depression, and may also be used together with antidepressant treatment. The current use of hypnotics in the general population is estimated to range between 3.5% and 11.7%, doubling in elderly populations-11. HypnHowever, the high rate of insomnia, EDS complaints, and psychiatric disorder in the elderly, their frequent comorbidity, and the potential risk of mortality associated with both sleep disorders and psycOverall, evidence suggesting an association between hypnotics consumption and mortality in the elderly remains controversial. Four observational studies in young adults,17 and eThe aim of the present study is to examine the associations between the use of hypnotics and 12-year mortality risk  in a large cohort of community-dwelling elderly people, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders, EDS, and insomnia complaints. The impact of duration and type of hypnotic treatment were also evaluated.Participants were recruited as part of the Three-City Study, an ongoing multi-site longitudinal study involving three French cities: Bordeaux, Dijon and Montpellier. BrieflyThe study protocol was approved by the ethical committee of the University Hospital of Kremlin-Bicêtre and CPP Sud Méditérannée III, and written informed consent was obtained from each participant. The participants were administered standardized questionnaires and underwent clinical examinations at baseline and after 2, 4, 8, 10 and 12 years.The exact date of death of the participants was obtained from death registries. The causes of death were collected by the local study centers from medical records and interviews with family physicians, clinicians and other non-medical informants (relatives or caregivers). A valid2). The presence of hypertension was defined by measured systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg or current antihypertensive treatment. Diabetes was defined as fasting glucose level ≥7.0 mmol/l or treatment for diabetes. Hypercholesterolemia was defined as total cholesterol level ≥6.2 mmol/L or treatment with lipid-lowering agents. Detailed medical questionnaires included past history of respiratory and thyroid disorders, and cardio-cerebrovascular disease  established according to standardized questions.The standardized interview included questions on demographic characteristics, level of education, living alone, and on health behaviors . Information on the health of the participants was obtained through detailed medical questionnaires. Case-level depressive symptoms were defined as a score above the 16-point cut-off on the Center for Epidemiological Studies-Depression Scale. Anxiety2), with frequent/often EDS, and frequent/often loud snoring.Sleep complaints were assessed at baseline as part of the clinical interview, followed by the completion of a specific sleep questionnaire. The parAt baseline and at 2, 4, and 8-year follow-up, an inventory of all prescriptions and over-the-counter drugs used during the preceding month was included in a standardized interview. Medical prescriptions and the medications themselves were checked by the interviewer, thus minimizing exposure misclassification. Current use of antidepressants and hypnotics were coded according to the World Health Organization’s Anatomical Therapeutic Chemical Classification. HypnotiP <0.15. Model 1 was adjusted for study center, age, and gender. Model 2 was further adjusted for education, alcohol intake, smoking status, BMI, confinement, respiratory disorder, cognitive impairment, history of CVD, hypertension, and diabetes. Two other models were adjusted for diseases associated with hypnotic use to take into account possible prescription bias, for example, number of insomnia complaints and EDS (model 3); and anxiety, depressive symptomatology, and antidepressant use (model 4). The multivariate model 5 was adjusted for all possible confounders. All-cause mortality was the principal outcome defined for the analysis. In secondary analyses, cause-specific mortality due to CVD and cancer was analyzed for separate end points. If both CVD and cancer were reported as cause of death, both causes were considered in the analysis. In all final models, significance level was set at P <0.05. Analyses were performed using SAS statistical software .Logistic regression models were used to compare the characteristics of participants according to the use of hypnotics at baseline after adjustment for study center, age, and gender. To analyze the associations between hypnotic use and risk of mortality, Cox proportional hazard models with delayed entry and age of the participants as the time scale were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI). This method gives better adjustment for age and is therefore preferable for a sample of elderly individuals over the standard model that uses study time as the time scale, because the covariates are strongly associated with age ,36. MultP <0.05 for all comparisons). They were also more likely to have died during the follow-up period (P <0.0001).As shown in the study diagram Figure , the stuAt baseline, 21.7% of the participants  were taking at least one hypnotic, 6.9% (n = 464) had three insomnia complaints, and 3.9% (n = 260) had no insomnia complaints. More than 3% (n = 212) reported taking two or more hypnotics. Regarding the main classes of hypnotics, 16% (n = 1070) took BZD, 4.8% (n = 321) BZD-like compounds, and 3.0% (n = 204) miscellaneous medications . With regard to duration, 4.8% (n = 304) had been taking hypnotics for less than 5 years, 3.9% (n = 244) between 5 and 10 years, 2.0% (n = 127) between 10 and 20 years, and 6.0% (n = 378) for more than 20 years.P <0.05 for all comparisons).Baseline sociodemographic and clinical characteristics of the participants according to hypnotic use are described in Table The median follow-up time for the study was 8.9 years with a range of 0.06 to 11.7 years. During this period, 1,307 (19.5%) deaths were observed. They were particularly related to CVD (26.3%), cancer (36.8%), and co-morbid CVD and cancer (3.1%). A substantial number of deaths were due to ill-defined causes (21.6%) as the result of multiple pathologies associated with frailty, and 10.2% died from respiratory diseases.P <0.15). Subsequent analyses were adjusted for these factors. A significant association was also found for participants at risk of OSAS .Baseline sociodemographic and clinical characteristics in relation to follow-up mortality  are given in Table P <0.01 for all comparisons, model 1). When potential lifestyle and chronic disorder confounders were entered into the model (model 2), the HR were reduced and failed to be significant except for BZD (P = 0.05) and this was unchanged when further adjusting for sleep complaints (model 3). When adjusting for anxiety and depressive symptomatology (model 4), the associations were not significant even for BZD (P = 0.22) and this was also the case for the complete multivariate model adjusted for all potential confounders (model 5). BZD-like compounds, and miscellaneous medications intake were not associated with all-cause mortality even in the minimally adjusted model 1. No significant interaction was found for mortality between hypnotic use and EDS, number of insomnia complaints, antidepressant use, chronic diseases, or being at risk for OSAS.Table P = 0.38).The relationship between hypnotic intake and the risk of mortality remained unchanged after exclusion of the participants who died during the first two years of follow-up n = 134), the follow-up rate at two years being 88%. With regard to specific causes of death, the use of hypnotics and BZD as well as number of hypnotics were associated with a significantly increased risk of CVD-related death in model 1, but not in the complete multivariate model adjusted for all potential confounders  did not report hypnotic use at baseline or at follow-up examination, 773 (14.5%) reported use both at baseline and at the first two follow-ups (persistent users) and 1,040 (19.6%) were taking hypnotics at one of two time points (intermittent users). The risk of mortality for the next 8 years was not significantly associated with the persistent use of hypnotics . Similar results were obtained when the analyses focused on persistent BZD users in comparison to non persistent BZD users or non BZD users.P-value ranging from 0.18 (model 1) to 0.76 (model 5) (data not shown).We also examined the impact of past hypnotic intake duration and compared participants who were not taking sleep medication at baseline with those having previously reported taking sleep medications for less than 5 years, between 5 and 10 years, between 10 and 20 years, and for more than 20 years. No significant association was observed between duration of hypnotic intake and all-cause mortality, the global This study examined associations between hypnotic intake and risk of excess mortality  over a 12-year period in a large elderly cohort, taking into account a wide range of potential confounding factors. As in several previous studies we observed significant associations between hypnotic use, notably BZDs, and mortality; however, these associations became non-significant after adjustment for all potential confounding factors, notably psychiatric disorder. These findings persisted even after taking into account up to 20 years duration of past hypnotic intake or persistent versus intermittent use.Previous studies have been inconsistent, with some studies observing significant relationships between hypnotic prescriptions and mortality,20-25,37Insomnia symptoms often lead to the use of hypnotics, a condition frequently associated with EDS, anxiety, and mood disorders. Depression and anxiety are also risk factors for mortality,15. DeprChronic use of hypnotic drugs, particularly BZD, may be associated with the risk of addiction and insomnia-rebound after withdrawal, psychomotor impairment and cognitive problems, OSAS, EDS, and car accidents,39,40. IAn increased incidence risk for cancer was also reported in individuals using hypnotics in some studies,22,24, eThe present study has some limitations. Unfortunately, data related to hypnotic dose were not available. Bias could have been introduced by the low participation rate at baseline and the non-random exclusion of participants with missing data at baseline – these participants were older, were more commonly hypnotics users, and more often had psychiatric and other chronic disorders that may limit the generalizability of our findings. Although unlikely, the possibility of overadjusment can not be excluded: potential confounding variables should be intermediate variables in the causal pathway between hypnotics intake and mortality. Finally, the absence of significant association between the use of hypnotics and mortality  after adjustments for covariates should be interpreted with caution regarding the small number of events per predictor variable.Our prospective study based on a large community sample has several strengths, including the duration of the follow-up and adjustment for a wide range of possible confounding factors including sociodemographic and lifestyle factors, chronic disorders, and sleep complaints as well as depression and anxiety disorders that were found as key confounding factors in this study. Prescriptions and medications themselves were checked by the interviewer and the causes of death were established by an independent committee. Finally, excluding participants who died during the first two years of follow-up did not modify the main results, suggesting a modest confounding effect of severe undiagnosed conditions in relation to hypnotic use and death.Our findings suggest that the use of hypnotics is not independently associated with an increased risk of mortality in the elderly, and that previous findings may be largely attributable to failure to take into account confounding variables, notably clinical co-morbidity, which is frequent at higher ages, particularly psychiatric disorders. Use of hypnotics might be a marker underlying more complex health issues.BMI: Body mass index; BZD: Benzodiazepines; CI: Confidence interval; CVD: Cardiovascular diseases; DIS: Difficulties in initiating sleep; DMS: Difficulties in maintaining sleep; EDS: Excessive daytime sleepiness; EMA: Early morning awakening; HR: Hazard ratios; ICD-10: International classification of diseases; OSAS: Obstructive sleep apnea syndrome.The authors have nothing to disclose in relation to this paper. IJ, MLA, KP, JS and AB report no disclosures. KR has received honoraria from Novartis and Glaxo Smith-Kline; is on the scientific advisory boards for the Biomedical Research Centre, King’s College London, and the MRC Strategic Steering Committee ; and serves on the editorial boards of the International Journal of Geriatric Psychiatry, Dementia, International Psychogeriatrics, Journal of Clinical and Experimental Gerontology, Psychogeriatrics, Neuronale, Neurologie-Psychiatrie-Gériatrie, and Gerontology. CB serves on advisory boards of the British Journal of Nutrition and Revue d’épidemiologie et de santé publique. YD has received speaker’s honoraria and support for travel to meetings from UCB Pharma, JAZZ and Bioprojet. YD participated in advisory boards of UCB Pharma, JAZZ and Bioprojet.IJ, MLA, and YD participated in the conception and design of the study. IJ conducted the analyses and wrote the first draft of the manuscript. IJ, MLA, AB, YD participated in the interpretation of the data. IJ, MLA, CB, KP, JS, AB, KR and YD contributed to the writing of the manuscript. MLA, CB, KP, JS, KR and YD participated in the acquisition of the data. All authors approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/212/prepub


This prospective study aims to identify and compare the incidence of bacterial contamination of hospital charts and the distribution of species responsible for chart contamination in different units of a tertiary hospital.All beds in medical, surgical, pediatric, and obstetric-gynecologic general wards (556) and those in corresponding special units (125) including medical, surgical, pediatric intensive care units (ICUs), the obstetric tocolytic unit and delivery room were surveyed for possible chart contamination. The outer surfaces of included charts were sampled by one experienced investigator with sterile cotton swabs rinsed with normal saline.Staphylococcus aureus (17.8%), Methicillin-resistant Staphylococcus aureus (9.3%), Streptococcus viridans (9.4%), Escherichia coli (11.2%), Klebsiella pneumoniae (7.5%), and Acinetobacter baumannii (7.5%). Logistic regression analysis revealed the incidence of chart contamination was 2- to 4-fold higher in special units than in general wards [odds ratios: 1.97–4.00].For general wards and special units, the overall sampling rates were 81.8% (455/556) and 85.6% (107/125) (p = 0.316); the incidence of chart contamination was 63.5% and 83.2%, respectively (p<0.001). Except for obstetric-gynecologic charts, the incidence was significantly higher in each and in all ICUs than in corresponding wards. Coagulase-negative staphylococci was the most common contaminant in general wards (40.0%) and special units (34.6%) (p>0.05). Special units had a significantly higher incidence of bacterial contamination due to Noting that most hospital charts are contaminated, our study confirms that a hospital chart is not only a medical record but also an important source of potential infection. The plastic cover of the medical chart can harbor potential pathogens, thus acting as a vector of bacteria. Additionally, chart contamination is more common in ICUs. These findings highlight the importance of effective hand-washing before and after handling medical charts. However, managers and clinical staff should pay more attention to the issue and may consider some interventions. Reducing healthcare-associated infection (HAI) remains a critical issue for clinicians and managers in hospitals and healthcare institutions all over the world. Correct hand washing has been proved the most effective way to prevent HAIs Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Pseudomonas aeruginosa, and Klebsiella pneumoniaeIt was previously shown that stethoscopes, white coats, keyboards, faucets, mobile phones, writing pens, case notes, medical charts, and even wrist watches can be contaminated by environmental or pathologic microorganisms such as methicillin-resistant This prospective study was conducted between January 1, 2010, and December 31, 2010, at a 1,000-bed tertiary hospital in Taipei, Taiwan. The study was approved by the Biosafety Ethics Board of Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation. Certain hospital units were excluded from evaluation. Medical charts in the psychiatry, hospice, and burn units were excluded because they were placed in a “discrete” pattern (kept on each bedside table) in contrast to the charts in other general wards and ICUs, where charts were placed in a “central” pattern (kept on a chart rack at the nursing station). Additionally, medical charts in the nursery were excluded because in the nursery of our hospital, the medical staff use case notes without a plastic cover, instead of medical charts. Otherwise, medical charts in general wards including medical, surgical, pediatric, and Obs-Gyn wards as well as charts in corresponding special units including medical, surgical, pediatric intensive care units , and obstetric units (including the tocolytic unit and the delivery room) were surveyed for possible contamination. The sampling time was from 9 a.m. to 11 a.m., immediately following the morning shift. In the study, basic information including hospital stay of the patients and also classification of the beds in general wards and special units were obtained from the department of medical affairs. The data “hospital stay of the patients,” retrieved from an administrative database in the department of medical affairs, only described the duration of hospital stay and were “de-linked” data without any identifiable patient information including the name, ID number, gender, age, occupation, telephone, e-mail, and address. Consequently, we did not have access to the patients, and the written informed consents of the patients  were not available.In our hospital, medical charts are handled and recorded mainly by the physicans and nursing staff. Due to different characteristics in different units, it is not clear how many times per day the charts are handled in each unit. We only know that the nurses in general wards and those in ICUs have the same frequency of shifts . Also, the physicians in general wards and those in ICUs have the same frequency of shifts (two shifts per day). All physicians and nurses need to handle the medical charts at least once per shift to finish the medical record. Medical charts in general wards and in ICUs are kept on the chart rack at the nursing station, where the charting is done. All the medical charts throughout the hospital are identical and are replaced every 5 years. Basically, medical charts are not specially wiped down unless there are extra instructions or changes of hospital policy.Considering the differences in frequencies of handling the charts, medical charts of patients who were not hospitalized were excluded in order to avoid selection bias. Furthermore, both of excessively short and long hospitalizations may be major confounders for sampling the medical charts. Since a longer hospital stay may increase the chance of contamination of medical charts, charts of patients who had been in hospital for more than two weeks were excluded. Except for patients in the delivery room with a usually rapid turnover rate, we also excluded patients hospitalized for <3 days. This is because in Taiwan, many minor surgeries or laparoscopic surgeries are performed on patients with a subsequent hospitalization for one or two days based on payment or insurance considerations. In such cases, the physicians and nursing staff often complete all their records including admission, progress and discharge notes at one time and medical charts are handled with low frequency. Otherwise, medical charts that met the inclusion criteria in the general wards and special units were totally collected by means of an ordinary survey rather than being selected according to the investigator's preference (highly selected samples) so as to avoid selection bias . In ordeS. aureus, the presentation of MRSA was further confirmed by antibiotic susceptibility testing using the disk diffusion technique.Samples were collected from the entire outer surfaces (plastic covers) of the hospital medical charts with sterile cotton swabs rinsed with normal saline by an experienced investigator wearing sterile gloves . Prior tThe outcome measures included the overall incidence of bacterial contamination found on hospital medical charts in all general wards and special units, the differences in incidence of bacterial contamination found on medical charts between medical, surgical, pediatric, Obs-Gyn general wards and their corresponding special units, the species of Gram-positive and Gram-negative bacteria on the contaminated medical charts in all general wards and special units, and the differences in distribution of bacterial species on the contaminated medical charts between medical, surgical, pediatric, Obs-Gyn general wards and their corresponding special units.2) test, the Fisher's exact test (for expected numbers <5) and the t test to compare differences in the characteristics and the results of the medical charts retrieved for sampling. Further analysis was performed using logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI) of the incidence of chart contamination in special units when compared to general wards (the reference group).Data were collected and analyzed using the SPSS statistical software package . The statistics we used in this study included descriptive statistics, the chi-square ; 9.16 days in medical wards compared with 9.31 days in the MICU (p = 0.476); 6.80 days in surgical wards verses 7.12 days in the SICU (p = 0.292); 5.52 days in pediatric wards compared with 5.80 days in the PICU (p = 0.529); and 4.36 days in Obs-Gyn wards vs 2.70 days in the Obs-Gyn special units (p<0.001). Except for patients admitted to Obs-Gyn wards, there were no significant differences in the average length of hospital stay between the patients in medical, surgical, or pediatric wards and those in their corresponding ICUs.The contamination rates of medical charts selected for sampling were 63.5% in all general wards and 83.2% in all ICUs (p<0.001); 66.0% in medical wards and 86.3% in the MICU (p = 0.004); 63.4% in surgical wards and 84.6% in the SICU (p = 0.042); 52.4% in pediatric wards and 90.0% in the PICU (p = 0.015); 51.5% in Obs-Gyn wards and 50.0% in the Obs-Gyn special units (p = 0.933) . With thStaphylococcus aureus , Enterococcus faecalis, Streptococcus viridans , Corynebacterium spp. , and Bacillus spp. , as well as the incidence of chart contamination by Gram-negative bacteria, including Sphingomonas paucimobilis, Pseudomonas aeruginosa, Escherichia coli , Klebsiella pneumoniae , Pantoea spp., and Acinetobacter baumannii , was significantly higher in special units when compared with those in general wards. In addition, the incidence of chart contamination by MRSA was significantly higher in special units (9.3%) when compared with that in general wards (4.0%). Using logistic regression analysis, we showed that the odds ratios of bacterial contamination in special units ranged from 1.97 [95% CI: 1.10–3.53] for S. aureus contamination to 4.00 [95% CI: 1.51–10.64] for K. pneumoniae contamination, and the odds ratio of bacterial contamination by MRSA was 2.50 [95% CI: 1.12–5.59] in special units when compared with general wards.The results of this study revealed that most medical charts were contaminated by bacteria . In addition, medical charts in medical, surgical, and pediatric ICUs were more likely to be contaminated than those in each corresponding general ward (p<0.05), with the exception of Obs-Gyn units. Our data suggest that the medical chart is indeed a possible vector of bacteria and also a potential source of infection. This is particularly true of medical charts in the ICUs. The plastic covers of medical charts can harbor potential pathogens. In addition to CoNS, other causative and opportunistic pathogens were found on the surfaces of medical charts and the risk of chart contamination by these pathogens was 2- to 4-fold [OR: 1.97–4.00] higher in special units than in general wards. The incidence of chart contamination by MRSA was also significantly higher in special units (9.3%) when compared with that in general wards (4.0%). Logistic regression analysis showed that the odds ratio of bacterial contamination by MRSA was 2.50 [95% CI: 1.12–5.59] in special units when compared with general wards. In this study, the incidence of MRSA colonization in special units (9.3%) was even higher than that (6.8%) reported previously Corynebacterium spp., and Bacillus spp., are common skin floras, and are considered relatively avirulent although they can be pathogenic in certain populations such as immunocompromised persons with prosthetic devices, intravascular catheters, or other implanted devices. In fact, CoNS has become one of the most common nosocomial pathogens in the hospital setting, and most species are multidrug- resistant Corynebacterium spp., and Bacillus spp., and focused on chart contamination by other organisms that are regarded as pathogenic. Our data showed that the contamination rates of medical charts selected for sampling were 32.7% (149/455) in all general wards and 65.4% (70/107) in all special units. Our re-analysis data indicate that chart contamination is still common even after exclusion of those deemed environmental flora.A number of organisms, such as CoNS, In order to explain the possible mechanisms underlying our data, we suggest that our results are related to the sources and the frequencies of “contact” within the wards or special units of the hospital. Medical charts are handled by physicians, nurses, and other medical staff while recording, looking-up and handing over to the next shifts. The charts are placed in nursing stations, in medical record rooms, or on the beds to be sent to examination rooms, operation rooms, or therapeutic rooms, and therefore are prone to bacterial contamination. In the ICUs, the use and manipulation of endotracheal and gastrointestinal tubes, which are possible sources of contaminants, may result in excessive bacteria transfer, contributing to a higher incidence of contamination of medical charts. This is not the case in Obs-Gyn special units, including delivery and tocolytic units, where endotracheal and gastrointestinal tubes are used less frequently. The lower rate of chart colonization (50.0%) on obstetric special units may also be related to the characteristics of the pregnant women, who are usually a younger, generally healthier patient population with less antibiotic exposure. In summary, strict adherence to appropriate hand–hygiene measures and avoiding the unnecessary use of indwelling catheters and manipulation of invasive devices may be relatively simple means of reducing the transmission or spread of bacteria.The study herein has a number of strengths, including its relatively large sample size and a high sampling rate of hospital charts. Overall, a total of 562 charts were sampled and the total sampling rate exceeded 80% . Our results are therefore robust due to minimization of possible errors that originate from the sampling process. To the best of our knowledge, this is the largest study of its kind to investigate the contamination of the hospital charts. Additionally, all bias resulting from the samples, from the investigator, from the sampling and measuring process were minimized as much as possible by the methods used. The patients in the two groups  were comparable in terms of their length of hospital stay because of these exclusions of patients with very short or longer stays. Therefore, any differences in colonization rates were not related to the duration of hospitalization. The fact that there were notable differences in average hospital stay but unremarkable differences in chart contamination between Obs-Gyn general wards and special units may be explained by the special characteristics of pregnant patients in Obs-Gyn special units such as the delivery room, in which there is usually a rapid turnover of hospitalization and less infectious sources. Nonetheless, the percentage of Obs-Gyn beds in total beds was low (45/681 = 6.61%), and this deviation should not affect the main result of the study.Our study has some limitations. First, we collected medical charts for sampling in a large hospital. Thus, generalization of the conclusions to smaller hospitals, local clinics, or other healthcare institutions like nursing homes should be made with caution. Second, some characteristics of the patients whose charts were sampled, including gender and age, were not considered in our study, and could affect the results. As a cross-sectional study, the last limitation concerns some uncontrolled factors varying with time and the change of medical policies or guidelines. A longer follow-up investigation could overcome this problem, and provide more precise results.In conclusion, the incidence of contaminated medical charts is higher in the special units  than in each of the corresponding general wards. Based on the finding that most hospital charts are contaminated by bacteria, our study confirms that a hospital chart is indeed not only a medical record but also an important source of potential infection. Hospital charts, together with stethoscopes, white coats, faucets, and keyboards, have the potential to act as vectors of bacteria. This fact highlights once again the importance of effective hand washing before and after handling medical charts, entering casenotes


Toxoplasma gondii, anti-Leptospira spp., anti-Brucella canis and anti-Brucella abortus in stray dogs housed in shelters at Umuarama city, Paraná, Brazil. In order to detect toxoplasmosis, indirect immunofluorescence assay (IFA) was performed, agglutination microscopic (MAT) test for leptospirosis and agar gel immunodiffusion (AGID) and buffered acidified antigen (BAA) tests for brucellosis.Leptospirosis, toxoplasmosis and brucellosis are diseases with worldwide distribution. Among stray dogs, these zoonoses are facilitated by direct contact with other animal species, by the habit of scavenging garbage and hunting in search of food, drinking standing water, smelling other animals’ urine, licking female genitalia and the sexual act itself. The objective of this study was to detect antibodies anti-Brucella canis.Of the 175 serum samples analyzed, 70.85% were considered positive for toxoplasmosis by IFA, 20% by MAT for leptospirosis and 2.85% by AGID for The serological results of this study showed that stray dogs housed at the private shelter are potential carriers of these three different zoonoses and contribute to the spread and maintenance of these etiologic agents in the urban area of Umuarama (PR), Brazil. Leptospira genus, which may affect diverse species of domestic and wild animals as well as humans. The transmission of this disease occurs by direct exposure to the urine or organs of infected animals, or indirectly when there is self-exposure to an environment contaminated with bacteria, such as standing water, wet soils, vegetation or fomites [Leptospirosis is an infectious disease caused by bacteria of the  fomites .Brucella spp. The transmission occurs among animals by sexual contact between infected males and females or by exposure to an environment contaminated with secretions and/or infected placental membranes [Canine Brucellosis is an infectious, chronic zoonotic disease whose etiologic agent is embranes .Toxoplasma gondii, an obligate intracellular protozoan that utilizes domestic and wild cats as definitive hosts. Infection occurs by ingestion of oocysts spread in the environment, by cysts present in tissues of intermediate hosts and by transplacental transmission through tachyzoites [Toxoplasmosis is caused by hyzoites .Leptospirosis, toxoplasmosis and brucellosis are diseases with worldwide distribution. Among stray dogs, these zoonoses are facilitated by direct contact with other animals, by the habit of scavenging garbage and hunting in search of food, by drinking standing water, smelling other animals’ urine, licking female genitalia and by engaging in the sexual act itself -6.In Brazil, different studies have shown the seroprevalence of leptospirosis, brucellosis and toxoplasmosis in stray dogs in the states of Minas Gerais, Santa Catarina, São Paulo, Rio de Janeiro, Bahia and Pará ,7-12. ThLeptospira spp., Brucella spp. and Toxoplasma gondii in stray dogs housed in a shelter at Umuarama city, Paraná state, Brazil.Considering the absence of regional data and the importance of these agents in causing these diseases in humans, the objective of this study was to detect antibodies against The town of Umuarama is located in the northwest region of the state of Paraná, Brazil. On the outskirts of the city, there is a private, philanthropic shelter maintained by staff and visitors; it collects dogs, cats and horses wandering around the city and forwards them for adoption.The cross-sectional study included all dogs – regardless of age, gender or breed – residing in the shelter for the period March-May 2011. All dogs were pre-assessed by veterinarians regarding their nutritional status, hydration, body temperature, and abdominal discomfort. Exclusion criteria were dogs that had fever, dehydration, cachexia, anorexia, diarrhea, vomiting or any other clinical signs detectable at the time of blood collection.Up to 10 mL of blood was collected from each dog, by a veterinarian, via jugular venipuncture. Blood samples were identified and forwarded to the Laboratory of Preventive Veterinary Medicine at UNIPAR where they were centrifuged to obtain serum. Each sample was divided into three aliquots and stored in sterile flasks, identified and kept at - 20°C until use. Serological tests were performed in the laboratories the Leptospirosis and Zoonosis and Public Health of the Department of Preventive Veterinary Medicine at UNIPAR and at Londrina State University (UEL).Toxoplasma gondii, the sera were submitted to indirect immunofluorescence assay (IFA) [To detect antibodies against anti-ay (IFA)  employinLeptospira spp. antibodies, the samples were subjected to agglutination microscopic (MAT / AMT) test [Leptospira at a 1:100 dilution were considered reactive and then diluted at a two-to-one ratio to determine the maximum positive dilution. The analysis considered the most likely serovar the one that presented the highest agglutination titer whereas those that showed co-agglutination between serovars at higher dilution were considered reactive only to Leptospira spp. [For detection of anti-MT) test , using tMT) test  in the Lira spp. .Brucella canis samples were submitted to an agar gel immunodiffusion (AGID) test using a commercial kit prepared with antigen (proteins and lipopolysaccharide) from Brucella ovis, REO198 sample, produced by the Paraná Institute of Technology - Tecpar. Samples were considered reactive when they showed a precipitin line between the well of the test serum and that of the antigen, as instructed by the manufacturer.To detect antibodies, the anti-Brucella abortus antibodies, all sera were subjected to a screening test using the Buffered Acidified Antigen (BAA) test [Brucella abortus 119–3 strain, pH 3.65 ± 0.05 at 8% concentration (Institute of Technology of Paraná-Tecpar). The test was considered positive when BAA macroscopic agglutination occurred.To detect anti-AA) test . The antWe collected blood samples from 175 dogs of indeterminate breed, including 31 males and 144 females, aged between about 06 months and 13 years. Only eight dogs were excluded from the study due to their poor physical condition at the time of blood collection.We detected 124/175 (70.85%) serum samples reactive for toxoplasmosis, 35/175 (20.00%) for leptospirosis and 05/175 (2.85%) for brucellosis.For toxoplasmosis, 124 (70.85%) samples were considered reactive in IFA, 35 (28.23%) at the titer of 16, 58 (46.77%) at the 64 titer, 22 (17.75%) at the titer of 256, eight (6.45) at the 1024 titer and only one (0.80%) at the titer of 4096; the gender distribution is shown in Table In relation to leptospirosis, 35 20.00%) samples were considered reactive in MAT, 24 (68.58%) had antibodies against one serotype: 10 (41.66%) samples positive for Canicola, nine (37.50%) for Bratislava, three (12.50%) for Tarassovi and two (8.34%) for Hardjo with titers of 100 to 800, while in 11 (31.42%) samples, antibodies against two serovars were detected simultaneously, thus enabling identification of the most likely serovar: Ten (90.90%) samples were positive for Canicola and one (9.10%) for Pyrogenes with titers between 100 to 12800  samples were considered reactive in AGID, compared with none in BAA. The prevalences of anti-Of the 175 samples analyzed, reactive samples showed mixed infections: 14/175 (8%) positive for toxoplasmosis and leptospirosis; 03/175 (1.71%) for toxoplasmosis and brucellosis and 02/175 (1.14%) for toxoplasmosis, leptospirosis and brucellosis.Due to close contact with humans, different incubation periods and the possibility of asymptomatic cases in dogs with some zoonotic infections, dogs play an important role in the maintenance of different infectious and parasitic agents in the environment and their possible transmission to humans, a situation that constitutes a public health concern, especially in relation to stray dogs.Different researchers have demonstrated the frequency of toxoplasmosis, leptospirosis and brucellosis in stray and domicilied dogs in different regions of Brazil, in order to characterize the epidemiology of these diseases at the study site ,6,11. HoT. gondii, ten (3.30%) presented an antibody titer of 16; 41 (13.70%) a titer of 64 and 27 (9.00%) a titer of 256, which are similar to the results of the present work; but no titers of 1024 or 4096 were detected. Yet in the state of São Paulo, in the city of Araçatuba [T. gondii, 44.00% presented a titer of 256, 12.00% a titer of 1024 and 4.00% a titer of 4096, levels higher than our current findings. The infection in dogs occurs mainly by ingestion of the infective form of the parasite. The oocysts of Toxoplasma gondii, after being eliminated in cat feces, sporulate in the environment and can contaminate food and water; cysts, in turn, are present in the tissues of intermediate hosts such as rodents, cattle, pigs, and others. Stray dogs are exposed to infection when seeking food by hunting small rodents or scavenging domestic waste, or when drinking pools of water on the streets.The finding that 70.85% of canines were considered positive for toxoplasmosis, exceeds the 65.55% and 26.00% seropositivity levels detected in stray dogs in Salvador (BA)  and Avarraçatuba , out of It is known that toxoplasmosis is one of most prevalent zoonoses worldwide whose infection rates vary according to socioeconomic and cultural features of different localities. In Brazil, the varied disease rates described reflect its large territory while its high occurrence is influenced by climate and sanitation issues and even cultural habits ,11. In tToxoplasma gondii indicates that the location studied provided ecological conditions to keep this parasite in its infective form for both canines and humans, with dogs in this case being useful as a sentinel for human toxoplasmosis [From the standpoint of public health, the prevalence of stray dogs infected with lasmosis .Additional epidemiological research on the parasite would be critical for its control .Leptospira spp. antibodies at 20.00%, 21.21% and 10.50%, respectively. These serological results may have been influenced by differences in the prevalence of animal leptospirosis in the respective locations, besides reflecting the study period, which may have provided higher or lower probabilities of infection occurrence in stray dogs.Seropositivity for leptospirosis in stray dogs in the present work was similar to the studies in Patos (PB)  and LondResearch studies have reported ,23 that In canine leptospirosis, animals can eliminate viable leptospires in urine intermittently over long periods, even when asymptomatic . In the For the most prevalent serovars, Canicola, to which 57.14% of samples were reactive, has great epidemiological importance since the canines are considered its natural host and the presence of the bacterium in urine is common in asymptomatic dogs infected with this serovar . The serBrucella canis. This result is higher than those found in São João da Boa Vista (SP) [Brucella canis[Brucella abortus in the BAA was justified by the non-exposure of stray dogs to potentially infected bovine and / or ingestion of raw milk, placental membranes or aborted fetuses contaminated, due to the permanence of stray dogs only in the urban area.As to brucellosis, 2.85% of samples were found reactive by AGID for sta (SP) , where tlla canis. The facBrucella canis in this study is sufficient to define the problem as epidemiologically important primarily due to the close contact of dogs with potential human owners, since this shelter houses animals are waiting for adoption.Thus, despite the low rate of brucellosis positivity in this study, the public health risk exists since we are studying stray dogs. The 2.85% presence of antibodies against Brucella canis infection was identified in 1969 [Brucella spp. is of fundamental importance in the local epidemiological study.The zoonotic feature of the  in 1969 , and the in 1969 . These rA concern that one should have in relation to stray dogs housed at the studied shelter is that toxoplasmosis, leptospirosis and brucellosis are diseases associated with workers who have frequent contact with possibly contaminated animals or their byproducts, which expose employees of the respective shelter to bacterial and parasitic infections. The awareness of the shelter employees studied, based on this research, is of great importance in the aspect of public health.The serological results of this study showed that stray dogs housed at the private shelter are potential maintainers of these three different zoonoses and contribute to the spread and maintenance of these etiologic agents in the urban area of Umuarama (PR). Preventive measures such as neutering, adoption and responsible ownership campaigns would be key to reducing this problem studied in the city and elsewhere in the country.This study was approved by the Ethics Committee for Animal Experiments (CEPEEA) of the University of Paraná (UNIPAR) under process number 20677/2011.The authors declare that there is no competing interest.MKPD and DDG provided the idea; MKPD, PHM, GT and DB collection of biological samples; FMRLM, AB, DB and FE realization of serology; DDG, JCF, ITN and RLF analyzed the data; MKPD and DDG drafted the manuscript, and all authors read and approved the final manuscript.


Aerobic physical capacity plays an important role in reducing morbidity and mortality rates in subjects with cardiovascular diseases. This action is often related to an improvement in the autonomic modulation of heart rate variability (HRV). However, controversies remain regarding the effects of physical training on cardiac autonomic control in healthy subjects. Therefore, our objective was to investigate whether aerobic capacity interferes with the autonomic modulation of HRV and whether gender differences exist.2: 22-38 ml/kg-1 min-1), moderate (VO2: 38-48 ml/kg-1 min-1) and high (VO2 >48 ml/kg-1 min-1.) We evaluated the hemodynamic parameters and body composition. The autonomic modulation of HRV was investigated using spectral analysis. This procedure decomposes the heart rate oscillatory signal into frequency bands: low frequency (LF=0.04-0.15Hz) is mainly related to sympathetic modulation, and high frequency (HF=0.15-0.5Hz) corresponds to vagal modulation.Healthy men and women (N=96) were divided into groups according to aerobic capacity: low (VOAerobic capacity, regardless of gender, determined lower values of body fat percentage, blood pressure and heart rate. In turn, the spectral analysis of HRV showed that this parameter did not differ when aerobic capacity was considered. However, when the genders were compared, women had lower LF values and higher HF values than the respective groups of men.The results suggest that aerobic physical capacity does not interfere with HRV modulation; however, the cardiac modulatory balance differs between genders and is characterized by a greater influence of the autonomic vagal component in women and by the sympathetic component in men. Low cardiorespiratory capacity is directly associated with an increase in the morbidity and mortality rates in both male and female subjects with cardiovascular diseases, regardless of the presence of other risk factors -3.In this sense, the increase in aerobic capacity through the regular practice of physical exercises has been suggested to be a non-pharmacological means to prevent or treat a number of diseases, mainly those characterized as chronic degenerative, such as hypertension, diabetes mellitus and obesity ,5.In fact, there is evidence that moderate-to-high levels of cardiorespiratory capacity reduce the risks of mortality resulting from cardiovascular diseases or other causes in both genders, and this cardioprotective effect is independent of age, race, adiposity or other health conditions ,6-9.Despite this evidence, the causes of reduced morbidity via practicing physical exercises, which increases an individual’s aerobic capacity, have not been completely elucidated yet. It is common to report the improvement in cardiac autonomic control as one of the adaptations responsible for this reduction ,11. HoweMoreover, some studies have reported that the higher level of aerobic capacity improves cardiac autonomic function in healthy subjects, suggesting the hypothesis that high-performance athletes have a better autonomic HRV modulation than sedentary subjects or those who practice physical activities for leisure and/or health reasons -19. AnotTherefore, the objective of the present study was to investigate whether different levels of aerobic capacity can influence cardiac autonomic modulation in healthy subjects and whether there are differences between men and women.2); the use of drugs or other addictive substances ; a diagnosis of asthma, sleep apnea, or hypertension (blood pressure > 140/90 mmHg); metabolic disorders, including diabetes, dyslipidemia, pre-diabetes, and diabetes types 1 and 2; the chronic use of medications or substances that might interfere with cardiac autonomic function or the cardiovascular system; and the presence of musculoskeletal disorders that would prevent the subjects from performing the evaluations.A total of 96 healthy subjects (53 men and 43 women), aged between 18 and 40 years, participated in the study. All subjects were normotensive and had normal cardiopulmonary function. The exclusion criteria were as follows: a high body mass . Finally, all the information regarding the athletic profile was compared with the results obtained from cardiopulmonary stress testing (ergospirometry).Prior to the experimental procedures, all volunteers were selected by anamnesis, which provided data regarding each participant’s physical fitness and health status. Regarding their athletic profile, the volunteers were questioned about their daily and weekly physical activities, including the type, frequency, and workload. All volunteers who were included in the “low aerobic capacity” group (sedentary) reported that they were not following any type of physical activity program and had only a small caloric expenditure in daily activities, such as walking and climbing stairs. All volunteers included in the “moderate aerobic capacity” (trained) group reported that they were following a physical activity program at the gym or outdoors once per day for 5 days per week, with an average time between 1 hour and 30 minutes and 2 hours. These volunteers were participating in amateur competitions, such as marathons, for recreational purposes and to maintain their health and quality of life. The volunteers included in the “high aerobic capacity” group (athletes) had daily training sessions (4-5 hours) divided into two periods (morning and night) 7 days per week to improve athletic performance. All volunteers in this group were elite athletes who had participated in national and international sports competitions in their respective modalities. The modalities practiced by both the “moderate” and the “high” groups were considered as 2max: 22-38 ml kg-1 min-1), moderate aerobic capacity (VO2max: 38-48 ml kg-1 min-1), and high aerobic capacity (VO2max: > 48 ml kg-1 min-1).After the screening, the selected volunteers were divided into three subgroups according to aerobic physical capacity, which was determined using a maximum ergospirometric test on a treadmill as follows: low aerobic capacity . All subjects were informed about the procedures and non-invasive experiments that would be performed in this study. After agreeing to participate in the study, all subjects signed an informed consent form.Each volunteer was evaluated in the morning (08:00 to 10:00 am) during two laboratory visits. They were previously instructed not to perform intense physical activity and to avoid the consumption of alcoholic and caffeinated beverages for 48 hours prior to testing, and to sleep at least 8 hours and eat soft food 2 hours before testing.Systolic arterial pressure (SAP), diastolic arterial pressure and mean arterial pressure (MAP) were obtained using a mercury column sphygmomanometer with the auscultatory method. Heart rate (HR) was obtained using an electrocardiographic digital recorder . Evaluations were performed before experimental procedures and after a 15-minute rest period.HR recordings for HRV spectral analysis via electrocardiograms  were performed between 9:00 and 10:00 a.m. for 40 minutes while volunteers were in a supine position. Time series were obtained from adjacent R-R intervals (iRR) and then divided into segments of 200 beats, which were superimposed over the segments of 100 beats obtained from the previous series. After calculating the mean and variance of each segment, a spectral analysis was performed using the autoregressive model . This pr2max) was assessed by a maximal exercise test on a treadmill  according to a previously published protocol [2 and CO2) was performed using a metabolic device .The maximum oxygen uptake .Body mass index values were obtained using the formula W/Hp<0.05. All statistical tests were performed with SigmaStat 3.5 software . The sample size calculation was performed using the “GraphPad StatMate 2.0”, confidence level of 95%, Power 80%, using the LF and HF variables in normalized units. It was been suggested the number of 12 volunteers in each group.The results are shown as the mean ± S.E.M. (standard error of the mean). The effects of gender and aerobic physical capacity were assessed by two-way analysis of variance (ANOVA). When appropriate, post hoc comparisons were performed using the Student-Newman–Keuls test. Differences were considered significant when : 27.9, p<0.001). In turn, the assessment of body fat percentage showed an inverse relationship with the level of aerobic capacity in both men and women. However, men had the lowest values at all levels of aerobic capacity. With regard to the hemodynamic parameters : 71, p<0.001). However, there was no statistically significant difference between men and women when the groups were compared. An inverse relationship was observed between aerobic capacity and AP in both men and women : 11.4, p<0.001; DAP, aerobic physical capacity factor, F: 7.78, p<0.001; MAP, aerobic physical capacity factor, F: 10.8, p<0.001). Additionally, women always demonstrated lower values than men : 18.9, p<0.001; DAP, gender factor, F: 13.3, p<0.001; MAP, gender factor, F: 18.2, p<0.001).The characteristics and hemodynamic parameters of the subjects are presented in rameters , both me: 6.89, p=0.010), smaller oscillations in the LF bands in the absolute : 15.6, p<0.001) and normalized : 15.8, p<0.001) units, and greater oscillations in the HF band in normalized units : 15.8, p<0.001) than men. In addition, the groups constituted of women had lower values of LF/HF ratio than men : 10.9, p=0.001). In turn, the level of aerobic capacity did not influence any of the spectral parameters evaluated in both men and women.This study investigated in detail the HRV and its relationship with aerobic capacity, addressing the differences between genders. The results of the present study show that higher levels of aerobic capacity improve the hemodynamic response, which was demonstrated by lower basal HR, SAP, DAP, and MAP values, independent of gender. However, women presented the lowest pressure values compared to men at each level of aerobic capacity investigated. Regarding the spectral parameters of HRV, the level of aerobic capacity did not induce any difference when same-gender subjects were compared to each other, although sinus bradycardia was observed in the high aerobic capacity group. However, when the comparison was performed between genders, there were differences at each level of physical conditioning.Recent studies have shown that moderate-to-high cardiorespiratory capacity is related to adaptations of several cardiovascular performance parameters, thus decreasing the risk of cardiac events and mortality ,23. In aAerobic physical training promoted important hemodynamic changes. In the present study, an accentuated sinus bradycardia was observed in high-performance athletes regardless of gender. In fact, sinus bradycardia is a phenomenon observed in athletes as a possible result of autonomic adaptations and/or intrinsic cardiac alterations, mainly involving the sinus node ,24. ThisAnother favorable effect on cardiovascular health resulting from an increase in aerobic capacity is a decrease in AP. Consistent with the findings reported in the literature, our study shows that the subjects with better aerobic capacity had AP values lower than those with poor aerobic capacity. The mechanisms involved in the physical training effect on AP are not completely elucidated. Some studies suggest the involvement of several mechanisms, such as changes in the activity of the autonomic nervous system, which is mainly characterized by a reduction in the sympathetic influence. An alternative mechanism involves a decrease of serum vasoconstrictor factor levels and an increase in the endothelium-derived dilator factor levels, resulting in a reduction in the peripheral vascular resistance, as evidenced by low levels of norepinephrine and plasmatic renin activity, resulting in an increase in endothelium-induced vasodilatation -28.Regarding the difference in AP response between genders, women showed lower SAP, DAP and MAP values than men, with women in the high aerobic capacity group having AP values smaller than those in other groups. The cause of such a finding is unknown; however, there are studies showing that women exhibit differences in several aspects of hemodynamic regulation compared to men. Among these aspects, one can cite low cardiac responses to baroreceptor activation, low plasmatic renin activity, increased vascular 1-adrenergic response and lower levels of circulating catecholamines compared to men -31. MoreThe present study demonstrates that the level of aerobic capacity does not promote changes in the spectral parameters of HRV when same-gender subjects were compared to each other. However, when men were compared to women, differences in each level of aerobic capacity were observed. Women presented the lowest values of LF oscillations and highest values of HF oscillations compared to their male counterparts, regardless of the level of aerobic capacity.Some studies have demonstrated that analyzing the HRV to quantify the modulating influence of both autonomic components  on the heart can also be an important tool in aiding the prognosis of cardiovascular stress and conditioning -43. In fIn this sense, the basal indices of cardiac autonomic modulation can be influenced by different conditions, including gender. When genders were compared, regardless of the level of physical conditioning, men presented an autonomic balance in favor of sympathetic modulation characterized by greater LF oscillations, whereas women presented an autonomic balance in favor of HF oscillations. These discrepant results were more evident in well-conditioned subjects , showing that gender can indeed influence cardiac autonomic modulation ,46-48. IRegardless of the differences between the genders observed in the present study, several studies have reported that practicing physical exercises regularly improves cardiac autonomic modulation, thus suggesting the hypothesis that athletes or well-conditioned subjects have a better pattern of cardiac autonomic modulation ,19. This2peak response and low basal HR, did not induce changes in the spectral parameters of HRV, which has also been corroborated by other authors [However, no alteration in cardiac autonomic modulation was observed in our study when the groups of subjects with different aerobic capacities were compared to each other, regardless of the evaluated gender. Thus, our results suggest that the aerobic capacity level, which is characterized by a greater VO authors ,24,56,572max [These discrepant results suggest that other components of aerobic physical conditioning may contribute to the difference in cardiac autonomic modulation in healthy subjects. For example, resistance strength is a determinant of aerobic capacity that is independent of the VO2max ,59. In a2max .Meanwhile, other mechanisms may have contributed to these results. Because of the presence of respiratory sinus bradycardia, as evidenced by low values of basal HR in the high aerobic capacity group and the absence of changes in the autonomic modulation of HRV, physical exercise may have played a direct role in the sinus node modulation in these subjects, although this parameter was not investigated in the present study.Our results suggest that cardiovascular and autonomic responses, regardless of the level of aerobic capacity, are different between men and women, as the former present a profile of cardiac autonomic modulation that favors the sympathetic component, whereas the latter present a profile that favors the vagal component. In addition, the level of aerobic physical capacity did not interfere with the autonomic modulation of HRV in the healthy subjects, despite the presence of sinus bradycardia in the groups with high aerobic capacity.