To determine the effects of high dietary protein and energy intake on the growth and body composition of very low birth weight (VLBW) infants.Thirty-eight VLBW infants whose weights were appropriate for their gestational ages were assessed for when they could tolerate oral intake for all their nutritional needs. Thirty-two infants were included in a longitudinal, randomized clinical trial over an approximate 28-day period. One control diet  and two high-energy and high-protein diets  were compared. Differences among groups in anthropometry and body composition  were determined. An enriched breast milk group (n = 6) served as a descriptive reference group.Groups B and C displayed greater weight gains and higher increases in fat-free mass than group A.An intake of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein increases fat-free mass accretion in VLBW infants. The Nutrition Committee of the American Academy of Pediatrics suggests that, with optimal care and nutritional support, the growth rates of very low birth weight (VLBW) infants should be similar to those of fetuses of the same gestational age . NeverthTo better define the macronutrient requirements of these infants, the increase in lean body mass should be taken into consideration in addition to weight gain. The ratio of lean body mass to fat mass in the weight gained depends on the protein and energy ratio in the diet. If energy and protein intakes are inappropriate, weight gain and the rate of increase in length and head circumference are reduced ; howeverThe aim of this study was to explore the effects of high protein (4.2 to 4.7 g/kg/day) and high energy  intakes on the growth and body composition of VLBW infants. Our hypothesis was that supplemented formula would be well tolerated and would increase weight and lean body mass in preterm infants compared to newborns who did not receive supplementation.Thirty-eight preterm (gestation of 32 weeks or fewer) newborns with weights below 1500 g and who were appropriate for gestational age were included in the study. The newborns were admitted to the neonatology ward of Hospital Clinic in Barcelona, Spain. Their baseline characteristics and complications of prematurity for each study group are shown in Table ® Human Milk Fortifier (Mead Johnson). Patients who were not breastfed were randomized to receive one of the three formulas detailed in Table ® (Nestle), was given to the control group . The two experimental groups received high-energy and high-protein formulas with different energy-to-protein ratios: 150 kcal/kg/d with 4.2 g/kg/d of protein for group B (n = 12) and 150 kcal/kg/d with 4.7 g/kg/d of protein for group C (n = 12). ProMod® (Abbott) and Duocal® (SHS) were used to increase the protein and energy contents of the preterm formula.Breastfed infants served as a reference group . The macronutrient content of breast milk in this study Table  was obta2 (in m).The weight, length and head circumference of each infant were measured by the same investigator every week for four weeks (approximately 28 days). Electronic scales, accurate to 1 g, were used to weigh the subjects. Length and head circumference were measured using non-stretch tape. Z-scores were calculated for each infant, taking into account sex and post-menstrual age, by applying neonatal growth curves from Catalonia, Spain, which contain data obtained from more than 200,000 newborns . Body ma® . The clinical methodology followed the recommendations of Tang et al. [Body composition was measured via total body electrical impedance analysis (BIA) and was performed by a single investigator. Impedance and resistance were measured using a Bioscan Spectrumg et al. . Skin el2 + 3.84 foot length2)/resistance. A fat-free mass (FFM) value was then obtained using the following equation: FFM = total body water/water percentage of the FFM. The water percentage of the FFM was based on the studies of Fomon et al. [Total body water was determined using the equation described by Tang et al. : Total bn et al.  and Ziegn et al. . Once thA longitudinal, interventional, randomized clinical trial was used. At the beginning of the study, the weights, lengths and head circumferences of the subjects with the corresponding Z-scores were determined, along with their BMIs, FMs and FFMs. Data regarding anthropometric values, gestational age at birth and previous illnesses were obtained from hospital records. For the four-week study period, the 32 patients fed artificial formula were randomly assigned to either high-energy and high-protein diets (groups B and C) or a standard energy and protein diet (group A). Serological control measures  were assessed once in each patient, during the third week of the study, to detect nutrition-related adverse effects in the three groups. The weights, lengths and head circumferences with their corresponding Z-scores, along with the BMIs, FMs and FFMs were determined on approximately Day 28 of the study and were considered the final values for the study.The sample size of each group was calculated according to the hypothesis that supplemented formula would increase FFM accretion. When the first five cases without supplementation (group A) and the first five supplemented cases (groups B or C) were analyzed on the 21st day of the study, their FFM accretions were 15.09+/-2.14 and 19.85+/-4.15 g/kg/day, respectively. Using these preliminary data, the sample size to compare two independently observed means by a bilateral analysis with 80% power and an α-risk of 0.05 was calculated to be 12 cases per group (10 cases plus 2 for possible drop-outs). Therefore, a sample size of 12 cases was considered suitable for each of the three groups.All the variables displayed normal distributions. The results were expressed as the means ± SD. Cross-sectional differences in anthropometric and body composition measurements among all groups  were tested by analysis of variance . In the UNIANOVA, the factor was the group, and the covariates were the initial corresponding figure and the duration in days of the intervention. If the p-value of the factor group was < 0.1, the UNIANOVA with covariates tests were repeated to see if a significant difference existed between any of the three paired comparisons . A chi-squared test was used to analyze the significance of the differences between qualitative variables. Statistical analyses were performed using SPSS 13.0 . The results were considered statistically significant at p < 0.05.There were no significant differences between groups in baseline characteristics or in incidences of the following complications related to prematurity: patent ductus arteriosus, intracranial hemorrhage, hyaline membrane disease, sepsis and necrotizing enterocolitis Table .Energy intake up to 150 kcal/kg/d and protein intake up to 4.7 g/kg/d were well tolerated by all subjects from both the clinical and analytical points of view. Analytical data by groups are shown in Table The corrected ages of the preterm infants and measurements of the weights, lengths and head circumferences, along with the corresponding Z-scores, are shown in Table At the end of the study, weight gain was greater in groups B and C than in group A . In addition, groups B and C exhibited significant increases in weight z-scores compared to group A . Length gains and head circumference gains were similar in all groups, but final head circumference was significantly higher in group B than in group A (p = 0.033). The greater weight gains observed in groups B and C were related to greater increases in FFM, which were significantly higher than in group A .Despite the greater protein intake in group C versus group B, there were no differences in weight gain or FFM accretion between these groups. Therefore, intake consisting of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein, with a protein/energy ratio of 2.8 g/100 kcal, was sufficient to achieve appropriate increases in weight and FFM in VLBW infants during their hospital stays.The breastfed group was regarded as a reference group for growth, FM accretion and FFM accretion. It was not considered in the statistical analysis because the intervention was only performed in formula-fed infants. Furthermore, the breastfed group happened to have the smallest children at birth. The weight differences at birth might have influenced the weight outcomes at the end of the study.Our results show that an energy-enriched formula with a sufficient amount of protein increases weight gain with greater FFM accretion compared to normal formula in VLBW infants of appropriate weight for gestational age. The results were obtained after controlling for the initial values of weight gain and FFM accretion and for the duration of the intervention. Bioelectrical impedance is a straightforward, non-invasive, relatively inexpensive and portable method for evaluating changes in body composition . Body coThe goal of nutrition in the VLBW infant is to optimize growth and neurodevelopmental outcomes while avoiding both short-term and long-term toxicity and adverse outcomes. Consistent with previous findings ,27,28, oIn this early period of life, catch-up growth in head circumference was detected in each group, as indicated by the positive Z-score gains in all three groups. In addition, when the growth in head circumference was controlled for its initial value and for the duration of the intervention, it was statistically higher in group B than in group A. Postnatal head growth is an important clinical indicator of brain growth. In fact, poor postnatal head growth in preterm infants is strongly associated with poor neurodevelopmental outcomes and cerebral palsy . TherefoCatch-up growth in intrauterine growth-restricted infants may increase their risk of obesity, hypertension, impaired glucose tolerance and cardiovascular disease. Therefore, there is a concern that accelerated growth during a critical period in preterm infants could lead to long-term adverse metabolic effects. A strength of our study is the inclusion of infants whose growth was appropriate for their gestational age, as these infants are metabolically different from intrauterine growth-restricted infants. The long-term effects of rapid growth of body weight on the onset of metabolic syndrome are relatively small compared to those of other risk factors . These data suggest that the type and intake of nutrition needed by preterm infants with intrauterine growth restriction may be different from that of preterm infants with growth appropriate for their gestational age ,34.The macronutrient composition of breast milk was based on reports rather than directly measured; therefore, there may be some error in the estimated macronutrient intakes. Although we had the appropriate number of newborns in the high-protein and high-energy groups , the number of newborns in the control group was less because four newborns were withdrawn from the study at the request of the parents. In addition, we were wary of administering high levels of protein to preterm infants due to the potential future risk of overweight or obesity, as has been reported in healthy, formula-fed infants . In a grThis study suggests that higher protein and energy intake during a critical period is advantageous for preterm infant growth and body composition because it increases weight gain, weight z-score and FFM accretion. Energy and protein intakes of 150 kcal/kg/d and 4.2 g/kg/d, respectively, are sufficient to increase FFM accretion.The authors declare that they have no competing interests.BIA: body electrical impedance analysis; BMI: body mass index; VLBW: very low birth weight; LBW: low birth weight; FFM: fat-free mass; FM: fat mass.JAC and JF were responsible for the study design and for writing the manuscript. JAC performed the anthropometrics measurements and BIA explorations. JF performed the statistical analysis. GR, RC and XC revised the manuscript. All the authors read and approved the final manuscript.


Cassia fistula is named in Traditional Iranian Medicine (TIM) as “Folus”.The prevalence of Pediatric Functional Constipation (FC) has been reported between 0.7% to 29.6%. This study was conducted to compare the laxative effect of A randomized clinical trial was carried on 81 children (age range: 4–13 years) with FC, according to Rome III criteria in Amirkola Children’s Hospital, Babol, Iran. They received CFE or MO randomly for three weeks. CFE was produced according to the order of TIM references. Children were counted as improved when they exited from Rome III criteria of FC. Frequency of defecation, fecal incontinence, retentive posturing, severity of pain, consistency of stool and anal leakage of oily material were compared between the two groups and with baselines. An intent-to-treat analysis was used. Safety of drugs was assessed with the evaluation of clinical adverse effects.41 children were assigned randomly to receive CFE and 40 children received MO. After three weeks of medication, 84% of children in CFE group and 50% in MO group (p = 0.002) exited from the criteria of FC, so called improved. All measurable criteria improved in both groups. The frequency of defecation in CFE group improved from 1.7 per week (before the study) to 10.6 per week (at the third week) while this parameter differed in MO group from 2 to 6.1 (p < 0.001). The severity of pain during defecation and consistency of stool improved significantly better in CFE group than MO group (p < 0.05), but there were not any significant differences between the two groups in fecal incontinence and retentive posturing. Anal leakage of oily material occurred as an important complication in MO group while the children in CFE group did not complaint it. Drug’s compliances were not significantly different in the two groups. CFE and MO did not cause clinically significant side effects.CFE was most effective than MO in the 3-week treatment of children with FC. Functional constipation represent the common problems in childhood . Constipcassia fistula . The different compounds of cassia fistula are found in TIM book references [Today, many people seek help from natural based drugs  and compferences ,10.Cassia fistula L. (Leguminosae) is cultivated in the tropics like the West Indies, Ceylon, China, Egypt, Amazon, Sri Lanka and many other countries, and is widely used in traditional medicine for children and pregnant women [nt women  as mild nt women . Its antnt women -16 and hnt women -20 have nt women ,21-26 annt women  have beecassia fistula has cathartic and laxative effect because of the anthraquinone derivatives isolated from the pulp of the its fruits [cassia fistula emulsion (CFE) by a formula of TIM [vs mineral oil (MO) that is the most commonly used lubricant laxative [Although, s fruits ,12,27, wa of TIM vs mineralaxative ,28 in thThis study is a clinical trial of 81 functional constipated children, referred to the Pediatric Gastroenterology Department of Amirkola Children’s Hospital , from June to September 2011.After obtaining informed consent from the parents, the children were divided through a systematic randomization into two parallel therapeutic groups: CFE and MO.The study was approved by the Ethics Committee of Shahed University and was registered in IRCT (ID: IRCT201107026932N1).The patients were treated for three weeks. The investigators, the children and their parents were aware of the study group assignment.Age between 4–13 years old and presence of FC were the inclusion criteria.Functional constipation was defined by a duration of ≥2 months of at least 2 or more of the following characteristics: ≤ 2 defecation in the toilet per week, ≥ 1 episode of fecal incontinence per week, history of retentive posturing or excessive volitional stool retention, history of painful or hard bowel movements, presence of a large fecal mass in the rectum, history of large diameter stools that may obstruct the toilet. These criteria are Paris Consensus on Childhood Constipation Terminology criteria  as Rome The children with inclusion criteria were visited by the pediatric gastroenterologist to provide complete FC criteria. If history and physical examination could not prove FC, paraclinics like anorectal manometry, thyroid function tests, anti-tTG, and other laboratory tests were performed. If it was confirmed to be FC and the parents were willing the children were entered to the study.Any symptom of organic constipation in the history, physical examination or paraclinics  -34. ScorThe parents learned to compare pain and consistency of stool everyday during the study with these scores. If the situation would have been better, the scores would be less than these scores, and so on.In physical examination, the presence of an abdominal fecal mass and/or rectal mass and any anal lesion such as fissure, hemorrhoid and fistula was examined.The treatments started with demystification. If any fecal mass was found, disimpaction was done with normal saline. Regular toilet sittings for 5 minutes after each meal and diet changes were recommended to all the children and then maintenance therapies in two groups were started.During every visit and phone call, the parents were questioned with respect to diarrhea, abdominal pain and cramps, anal leakage, exacerbation of constipation, nausea and vomiting, dermatologic complaints, weakness, edema, palpitation or any other adverse effects.Clinical efficacy and tolerance were assessed using weekly sheets, parents completed every night. They were given three sheets (included seven questions in seven columns) to complete them daily for 3 weeks.The parents were asked to complete the following: episodes of defecation, fecal incontinence, oily leakage and retentive posturing per day. If the defection occurred at least once a day, the average of severity of pain and consistency of stool would be written compared with what declared in the beginning of study.In addition, the parents were asked to explain the acceptance and tolerance of drugs on the bases of our definition, from numbers 1 to 7: taking drug, with willingness, score 1. Taking with no resistance, score 2, and with objections, score 3. Taking with objection and also allurement, score 4. Taking forcefully, score 5. Does not easily take it by force, but tolerate it, score 6. Vomiting, if anyway takes it, score 7.These concepts and scores were exactly defined and explained to the parents. In every phone call, they were asked to repeat these definitions and talked about them again to achieve their unique meaning. Once every 2–3 days we called up the parents, and if it was necessary and possible spoke with the child. In these calls, they were asked about filling out forms, therapeutic effects and any side effects of the drugs. If there were any serious questions or problems, we visited the child. In average, each child in the course of study was visited three times and had six phone calls.At the end of 3 weeks of treatment, the children were visited by the pediatrics gastroenterologist. The filled out sheets were evaluated. If there was a serious mistake in filling out the forms, after explaining it, they were corrected by the parents.cassia fistula was purchased from local herbal drugs market in Tehran, Iran, and was identified by Herbarium of the Faculty of Pharmacy, Tehran University of Medical Sciences, where the specimens of cassia fistula were deposited under the voucher No.PMP-618. The dried fruits were cut into pieces and after isolating the seeds, they were soaked in sterile water. Then with a filter, the aqueous solution of cassia fistula was separated from the other parts. The solution was concentrated with heat and under reduced pressure and during concentration (according to TIM reference [cassia fistula.The dried fruits of eference ) sugar aThe children received initially either 1 ml/kg/day MO  or 0.1 g/kg body weight daily of CFE.cassia fistula, the daily dose of 4–8 gram of fruit pulp is recommended [In Physicians’ Desk Reference for Herbal Medicines for ommended . In TIM ommended .cassia fistula) in a pilot study. After this stage, it seemed that the effective safe dose of emulsion was 0.1 g/kg. So we started to prescribe it and adjust the dose every 3 days by calling up the parents. The parents were provided with guide. The results of the study lines regarding on how to adjust the dosage of medication. In case of diarrhea, the dose was reduced 25%, and if it did not respond well to medication, the dose was increased 25%, all just for one time. MO was prescribed twice daily and CFE in three-separated doses .To obtain an effective dose of CFE, it was used in a step-by-step increasing manner in 3 adults and then 5 children from the dose of 0.05 g/kg , and analyzed. Efficacy analyses (improved and not improved) were performed with the intent-to-treat population, defined as all children assigned randomly. Defecation frequency, episodes of fecal incontinence, anal leakage of oil, retentive posturing, severity of pain and consistency of stool were calculated from the available follow-up data. Comparisons were made between the initial data and the follow-up data, between the first, second and third weeks follow-up data, and within the groups. The statistical analyses included the determination of means and SDs, t test, χFrom June to September 2011 among the 235 patients visited for constipation, 81 patients with FC which included 52(64.2%) boys and 29(35.8%) girls gave their written informed consent and were then randomized to receive the CFE or MO. All patients were followed-up for 3 weeks. The last follow-up visit of the patients treated in both groups was in September 2011. Figure The baseline characteristics of the patients in two treatment groups were similar Table . The ageIn this randomized, controlled, clinical trial in children with constipation, CFE was more effective than MO for the treatment of FC.In all our criteria, both drugs were effective. In fecal incontinence and retentive posturing, the results did not have any significant differences between the two groups. However, improvements in defecation frequency, severity of pain and consistency of stool were significantly better in CFE group.In addition, even though oily leakage increased as a complication of MO, it did not occur in the CFE group at all. Therefore, lack of this complication is one of the most important advantages of CFE rather than MO.In qualitative comparison between the two groups, improvement (exit from the criteria of FC) was significantly better in CFE group.The details of quantitative results are in Figures As a qualitative comparison between the two groups, in the 1-week follow-up visit, 43% of the children in the CFE and 39% in the MO group showed improvement .These rates of the 2-week follow-up, were 62% in CFE group and 41% in MO group. After a 3-week follow-up, the improvement rate was significantly better in CFE group, so that 84% in this group exited from the criteria of functional constipation, but improvement in MO group after 3 weeks was 50% (p = 0.002). The details are in Table As we had known, anal leakage of oily material was the most common complication of mineral oil . It occuIn CFE group, no cases withdrew due to adverse effects.In MO group, four patients did not complete the total duration of medication. A girl (66 months old (m/o)) withdrew after two weeks because of anal leakage of oily material for more than 20 times per day. Two patients withdrew using MO because of lack of response (A boy of 54 m/o after 2 weeks and a girl of 65 m/o after 1 week).In addition, a girl of 62 m/o withdrew taking MO after 2 weeks because of drug intolerance due to fever and upper respiratory infection.The average of compliance of drugs in two groups was not significantly different Table . Three pOnly one patient (52 m/o girl) in CFE group missed to be followed-up. We mentioned her FC clinically. Nevertheless, she did not use the drug at all, and had gone to another center, underwent rectal biopsy, ruled out Hirschsprung disease and began to use poly ethylene glycol (PEG).Cassia fistula has been used more than ten centuries in TIM [cassia fistula are potent phenolic antioxidants such as anthraquinones, flavonoids and flavan-3-ol derivatives [s in TIM ,10,37-39ivatives . Anthraqivatives ,27.MO or liquid paraffin that was used in control group, is the most commonly used lubricant laxative ,28. It iAlthough constipation is a common chronic problem, there are very few studies with children comparing using different laxatives . ConsequIn a comparative study by Urganci N et al., MO was more effective than lactulose in treatment of 40 children with constipation. It responded more rapidly and showed fewer side effects . In anotcassia angustifolia) and cassia fistula are both anthranoid laxatives [cassia fistula[Martinez-Costa C et al., used MO accompanied with senna in 62 children. Satisfactory results were achieved 1 month later in 32% of the children, 3–6 months later in 71%, and 6–12 months later in 85% . Clinicaaxatives  but the a fistula.Although PEG is now one of the choices of drugs, studies are not absolute. Attar A et al., in 1999 compared a low dose PEG 3350 with lactulose. Their results were not conclusive but they said that low dose PEG 3350 was more effective than lactulose and better tolerated . In 2002Although there is not any unique definition and criteria for FC, we used criteria of Rome III as inclusion criteria and for measuring qualitative outcome of the results. Our quantitative outcome measures were well defined by the use of these criteria.For entering in the study, three steps of explanation, disimpaction and maintenance therapy were performed. Also for disimpactions, we had different choices, but we used enema with normal saline that has been effective in relieving fecal impaction .Close follow-up was one of strength of this study. We called up all the parents every 3 days and talked with them about their children and in case of any changes in their bowel movement habit and other medical problems. Therefore, all of them trust us and because of this good follow-up, we missed only one patient during the study.cassia fistula was used in children, we should be very careful about it and its probable complications.In this study, like more other studies in this subject, it was not possible to perform a blind study because these two drugs have different colors, tastes and smell and were administered to children in different ways. Also, because it was the first time Another issue in this study was the age of the children entered into the study. Because we were not confident of the safety of drugs, we preferred children older than 4 years for our study. This problem led to a large number of children referred not able to complete the inclusion criteria.On the other hand, this age of entrance caused most children entered into the study to be visited by pediatricians, before. Most patients have already received medication, but mostly without good result. Some of these patients were refractory to the treatment.Probably, if the drug would have been used in younger children and as first choice, we could have had better responses and a lower dose of drugs might be needed.Our baseline characteristics of patients in the two groups were well matched. They were similar to other literatures  except iA short follow-up period is a limitation of our study. One reason for this matter was that, in this study we wanted to demonstrate the effectiveness of CFE as a new drug in the treatment of FC but the Ethics Committee did not permit us to deprive the children from the usual treatment, longer than 3 weeks. This short period of follow-up is current in the first studies in other drugs in this field, for example, this period for PEG was 2 to 4 weeks ,47. It wcassia fistula.In our study, since the drug dose in patients with CFE was 0.1 g/kg/day, most of our patients had previous medications and might have drug resistance to some extent, so we recommend to the patients to start 0.08 to 0.1 g/ kg/day, based on dried pulp of fruits of There was no significant difference between the compliance of the two drugs in three weeks. The acceptance of MO in three weeks did not differ significantly, but the acceptance of CFE in the first and second week was less, but in the third week, it was better. It might be because the children found it effective and tolerated its taste.cassia fistula emulsion) to be used for treatment of FC , although further researches about its safety should be done. Comparison with other laxatives such as PEG and senna for longer time is recommended.We offer CFE (Cassia Fistula Emulsion; MO: Mineral Oil; TIM: Traditional Iranian Medicine; RCT: Randomized Clinical Trial; VAS: Visual Analog Scale; PEG: Poly Ethylene Glycol.FC: Pediatric Functional Constipation; CFE: The authors have no competing interests.SAM, designed and performed the research, produced the cassia fistula emulsion and wrote the paper. MN, designed the research and wrote the paper, formulated the emulsion. MRE, designed and performed the research. MK, produced the cassia fistula emulsion. AB, designed the research, analyzed the data. All authors read and approved the final manuscript.


To Assess changes in infective endocarditis (IE) epidemiology over the last 5 decades. We searched the published literature using PubMed, MEDLINE, and EMBASE from inception until December 2011. Staphylococcus aureus (SA) in the last decade . Streptococcus viridans (SV) and culture negative (CN) IE frequency decreased over time (p<0.001), while enterococcal IE increased in the last decade (p<0.01). Patient age and male predominance increased over time as well. In subgroup analysis, SA frequency increased in North America, but not the rest of the world. This was due, in part, to an increase in intravenous drug abuse IE in North America (p<0.001). Among population-based studies  no significant changes were found. Einstein Medical Center, Philadelphia, PA were also included. Criteria for inclusion in this systematic review included studies with reported IE microbiology, IE definition, description of population studied, and time frame. Two authors independently extracted data and assessed manuscript quality. One hundred sixty studies  met inclusion criteria. Among hospital-based studies  staphylococcal IE percentage increased over time, with coagulase-negative staphylococcus (CNS) increasing over each of the last 5 decades (p<0.001) and Important changes occurred in IE epidemiology over the last half-century, especially in the last decade. Staphylococcal and enterococcal IE percentage increased while SV and CN IE decreased. Moreover, mean age at diagnosis increased together with male:female ratio. These changes should be considered at the time of decision-making in treatment of and prophylaxis for IE. Infective endocarditis (IE) extols a high cost for society worldwide, with a US incidence of 10,000 to 15,000 cases each year, and impRisk factors for IE have changed over time. There have been widespread changes in health-care delivery in the last five decades, which have impacted the clinical spectrum of IE. These include the use of intracardiac devices, prostheIn recent decades, several studies have noted an increase in the proportion of IE caused by staphylococcal species,15. HoweProper understanding of IE epidemiology is paramount, as different organisms produce varied complications and may require different treatment and prophylaxis. The objst, 2011. We supplemented the search with references from articles reviewed and correspondence with other researchers, including experts in the field. When a reference was deemed potentially suitable for inclusion, a full-text copy was obtained and reviewed according to predefined criteria (listed below). We followed the PRISMA guidelines for systematic reviews. We searched, with no language restrictions, PubMed, OVID/MEDLINE and EMBASE electronic databases from their inception to December 2011, for studies reporting infective endocarditis microbiology. We used the term ‘infective endocarditis’ for the Mesh keyword. Date last search performed was December 1Prospective and nonprospective studies reporting the frequency distribution of infective endocarditis in the last five decades were included in this systematic review. Two investigators had the protocol for study selection (LS and CD) and independently assessed the studies for eligibility. Inclusion criteria were: (1) a clear definition of the population studied; (2) a clear definition of the time period; (3) a clear definition of infective endocarditis; and (4) a clear description of the frequency distribution of the microbiology encountered. In order to avoid bias, we excluded studies limited to specific populations (e.g. HIV or intravenous drug users). When there was difference of opinion, a third investigator (NC) resolved the disagreement. The authors are fluent in English, Spanish, Portuguese, and Italian; papers in other languages were translated by collaborating physicians who were native speakers. When two studies reported data from the same cohort and time frame, only the most complete one was included. If a study reported data for various time frames, data were analyzed separately for each decade. Kappa (k) for inclusion was calculated from a sample of 10 randomly selected papers. Results were compared and inconsistencies were resolved by consensus. Dr. Andrew Wang from Duke University was consulted for reviewing the list of included studies for completeness.Staphylococcus aureus (SA), coagulase-negative staphylococcus (CNS), enterococci, Streptococcus viridans (SV) and culture negative (CN) IE. For each study included, the following information was extracted: first author’s last name, journal, year of publication, IE definition used, certainty (possible IE vs. definite IE), countries, time-frame, multi-center vs. single center, sample size, age, gender, mortality, intravenous drug abuse (IVDA), intracardiac device or prosthetic valve, We also included patients from Einstein Medical Center (EMC), a tertiary 440-bed city hospital in Philadelphia, PA, US; for the years 2000 - 2010. Data were retrospectively extracted per ICD code and then included only if patients met ‘definite’ or ‘possible’ modified Duke criteria. ClinicaTwo reviewers (LS and CD) independently assessed the quality of the manuscripts using the approaches recommended by Khan and colleagues and Stro2 test were used to compare studies by decades. Each group was compared to the rest using paired Students t-tests. Samples were weighted for size. Results from our own hospital were included in the last decade and weighted for size. Sensitivity analysis showed that subtracting this data did not affect results statistic significance. Moreover subtracting the biggest study by Murdoch et al. from the International Collaboration on Endocarditis did not affect statistical significance of results. Sub-analyses were performed for continent and IVDA. Correlation between IVDA and SA was performed using Spearman correlation test. Hospital-based studies and population-based studies were included. As both types of studies may be prone to bias  and collected on an Excel spreadsheet. Data were allocated to a decade according to the midpoint date for the time frame studied. For example if the time frame was 1979 to 1983, data was assigned to the 80s. Results are shown as mean +/- SD, percentages for each decade, and the 95% CI. Main variables studied were the frequency distribution of pathogens, patient age and gender, and in-hospital mortality. ANOVA and Chirral bias and popuData were presented in a graph as mean  and variance (size of diamond) for each variable studied in each decade, with standard deviations (blue). Each dot in a column represents a particular study percentage. N below decades represents total number of patients in each decade. Every patient included in each study was diagnosed with IE as described above. Candidate studies included 24,415 articles identified in PubMed, 10,421 in Medline, and 4,528 in EMBASE; one hundred sixty studies met all inclusion criteria . SV IE frequency distribution also decreased significantly in Asia  while in Europe there was a decrease that did not reach statistical significance (p=0.06). No significant changes were seen in Latin America and Oceania . Insufficient data were available from Africa for separate analysis. Subgroup analyses for changes in IVDA IE percentage are shown in In-hospital mortality rate due to IE decreased following the 1960s and remained stable thereafter  and 23.0% Methicillin-resistant Staphylococcus aureus (MRSA)] while CNS was seen in 6.9% of the cases. Enterococcus was the IE etiology in 19.2% and SV 9.6%. Culture negative IE represented 3.8%. Removal of this data did not modify overall results. We identified a total of 261 cases from 2000 to 2010 . Mean agThe main finding of this study is that the epidemiology of IE has changed worldwide over the last half century. Furthermore, the observed changes in IE microbiology varied by continent. These findings stemmed from analyses of hospital-based reports. In a separately analyzed smaller group of population-based studies (most of them from the US), no consistent changes in IE microbiology frequency distribution over time were observed. Most notably, the global percentage of SA IE has nearly doubled in the last five decades (18% in the 1960s to nearly 30% in the 2000s). When analyzed by continent this increase was largely due to an increased frequency of SA in North America (from 25% in the 1960s to 52% in the 2000s) with no significant change among reports from other continents. This finding has important implications as SA infections are associated with longer length of stay, higher death rates, increasThe present study also documents a substantial decline in the frequency of SV IE over the last five decades (27.4% in the 1960s to 17.6% in the 2000s). This finding was statistically significant for North America and Asia with a strong trend in Europe. Therefore, it appears that changes in the epidemiology of this organism are more widespread than for SA. Paralleling the increase in SA IE frequency, there was also an increase in CNS IE percentage over time. It is known that CNS infections are often related to the use of intravascular catheters and prosthetic vascular grafts. Thus, tEnterococcal IE frequency increased in the last decade of the study. Enterococcal infections typically affect elderly patients and those with prior valvular damage, diabetes mellitus, indwelling catheters, or who are on hemodyalisis. This fiWorldwide, the present study found increases in age among IE patients. This has important implications for treatment and use of health care resources as elderly patients have more comorbidities and may be more prone to infection with certain organisms, such as enterococci. Consistent with the general perception, the preA limitation of the present study is the lack of individual patient level data. This data was not available from older studies and including it for only the last decades would have changed one bias for another one, without adding accuracy. Another limitation is that most of the findings come from hospital-based studies, whereas no significant changes were seen in the population based-studies over time. One possible explanation for this is a lack of power . Population-studies are also subject to sample bias: the population studied may not truly represent the general population. They can be subject to underreporting, as many times they rely on surveys. Moreover, population-studies of IE in the US are mainly from the Olmstead County, a population that is unlikely to represent the total US population. Hospital-based studies can suffer from referral bias as well, with sicker patients being referred to specialized centers. Thus, these results might not apply to community hospitals. However, Kanafani and colleagues found onThe present study represents the largest systematic review of IE epidemiology to date. Important findings include an increase in staphylococcal IE frequency over the last half-century, particularly in North America, and a worldwide decrease in SV IE percentage. In the last decade SA IE and enterococci IE frequencies have increased while culture negative IE has decreased. Patients with IE are getting older and the male to female ratio is increasing. Mortality has changed little in the last four decades. Checklist S1(DOC)Click here for additional data file.


Pinus spp. grown in southern Brazil trees in different diameter classes and ages were used to demonstrate the correlation between BEF and R, and forest inventory data, such as DBH, tree height and age. Total dry biomass, carbon stock and CO2 equivalent were simulated using the IPCC default values of BEF and R, corresponding average calculated from data used in this study, as well as the values estimated by regression equations. The mean values of BEF and R calculated in this study were 1.47 and 0.17, respectively. The relationship between BEF and R and the tree measurement variables were inversely related with negative exponential behavior. Simulations indicated that use of fixed values of BEF and R, either IPCC default or current average data, may lead to unreliable estimates of carbon stock inventories and CDM projects. It was concluded that accounting for the variations in BEF and R and using regression equations to relate them to DBH, tree height and age, is fundamental in obtaining reliable estimates of forest tree biomass, carbon sink and CO2 equivalent.The Biomass Expansion Factor (BEF) and the Root-to-Shoot Ratio (R) are variables used to quantify carbon stock in forests. They are often considered as constant or species/area specific values in most studies. This study aimed at showing tree size and age dependence upon BEF and R and proposed equations to improve forest biomass and carbon stock. Data from 70 sample  CDM (Clean Development Mechanism) enables developing countries to participate in global efforts to reduce greenhouse gases (GHG) concentrations in the atmosphere and to accomplish the Kyoto Protocol commitments. However, few A/R CDM approved methodologies were available until recently and hence a small number of PDDs (Project Design Documents) were submitted to the CDM Executive Board (EB) of the UNFCCC (United Nations Framework Convention on Climate Change). One of the main constraints to proposing an adequate A/R methodology and applying it in a PDD is the difficulty in identifying and monitoring the complex biological relationships in a forest plantation as well as obtaining reliable estimates of biomass and carbon stocks. In recent years, several methodologies have been approved by the EB that allow us to obtain stock change estimates for large forest areas, but they are complex and difficult do apply.2 removal for a CDM project for the duration of a crediting period.There are different approaches to calculating biomass and carbon stocks in forests. These are mostly based on forest inventory information as well as various factors, referred to as biomass factors, or biomass equations, which transform diameter, height or volume data into biomass estimates . The calEstimates of biomass and carbon stocks from bole volume and wood density generally require the application of a biomass expansion factor (BEF) or biomass equations to obtain the aboveground and total biomass -5. BecauBEF and R application may also vary from project to project. Single default values are often used, as in Kauppi et al. 1992) , Kauppi 92 , Kaupi.e. IPCC default values of BEF and R [This study deals with the analysis of correlations of BEF and R with some typical tree inventory data  and the development of mathematical modeling relating BEF and R to the more easily obtained tree measurement variables. In this paper a comparison of three different approaches to estimate biomass and carbon stocks is carried out,  , for thrRegarding R, the mean value found in this study was 0.17, varying from 0.05 to 0.63. This means that on average, belowground biomass corresponds to 15% of the total biomass. The mean default value for pine in the Tropics is R = 0.32, according to IPCC, though a range of 0.24 to 0.50 in this ratio has been reported . In the It is noteworthy to mention that both BEF and R figures given by the literature are influenced by the methodology used in each case. Some authors adopt the definition of bole as the main tree trunk up to a minimum diameter. A BEF figure from bole of 4 cm minimum diameter is obviously rather smaller than another calculated from 10 cm minimum diameter. It is more problematic for broadleaf species that have sympodial growth than for pines with monopodial crown architecture. Similarly, R is affected by the depth and fine root dimension approach utilized. Deep root excavations and fine root dimension imply in greater root-to-shoot ratios given same conditions.Pinus species studied here, though it will be discussed at greater length later in this paper.As can be seen later on in this paper, BEF and R are correlated with DBH, height, and age, but the relationship among them is hardly constant. On the contrary, as the trees grow and advance in age the contribution of foliage and roots to the total biomass diminishes in both The correlation analysis performed on the biomass expansion factor and the root-to-shoot ratio, tree diameter, height, and age indicated that BEF and R have significant correlations with the tree measurement variables, as shown in Table The correlation matrix indicates that DBH is the variable more closely associated with BEF, followed by height and age, respectively, and that all of them have significant correlations. In contrast to the findings of this study, Levy et al. (2010) , Brown &On the other hand, R was more closely correlated with height, though age and DBH were also significant. BEF and R were also correlated with each other in this study, but the correlation coefficient was moderately smaller. The correlation between BEF and R seems reasonable, since trees need more root biomass to support a proportionally large crown.The results showed that biomass expansion factor and root-to-shoot ratio vary considerably with tree size (DBH and height) and age. The relationships are shown graphically in Figures This trend may be explained by the physiological maturation of trees , which rHowever, there was noticed heterogeneity of variance in BEF and R along tree size and age axes. This may be explained by the so-called Jensen's inequality, which describes how variance depresses the response variable in decelerating functions and elevates the response variable in accelerating functions ,29. The Eucalyptus. According to the authors the decline was primarily caused by a decline in canopy carbon gain and secondarily by a shift in the annual partitioning of gross primary productivity to belowground allocation and foliage respiration.On the other hand, Magnani et al. (2000)  tried toFigure Similar results were also reported by Lehtonen et al. (2004) . Soares Table The coefficient of determination for the 12 equations tested to estimate BEF ranged from 0.44 to 0.78, whereas for R stayed between 0.35 and 0.59. The standard error in the estimate for BEF equations ranged from 15.60 to 24.20%, whereas for R equations varied from 39.72 to 48.84%. When these two statistics of goodness of fit were taken into consideration, equation 12 was selected as the most accurate, though models 1, 2, 3, and 11 also presented similar performance. Equation 12 was also the most accurate for R estimation, though its mathematical formula differs from the BEF model, because both equations were fitted by means of stepwise regression. A graphical analysis of residuals performed on the 12 equations to estimate BEF and R confirmed those findings , estimates of total biomass (dry aboveground + belowground biomass), carbon stock and CO2 equivalent were generated by the three different approaches, as described before  and R (0.17) from the field data the estimates would be 335.69 t/ha, 137.63 tC/ha, and 504.66 tCO2eq./ha, respectively for total biomass, carbon stock, and CO2 equivalent. The difference between the estimates for these two approaches was less than 1%. However, when the calculations are made using regression equations the figures change drastically, to 251.32 t of total biomass, 103.04 t C/ha, and 377.82 t CO2eq/ha. Under this condition, the percentage difference in the estimates rises to 33%.Growth and yield was simulated for a 1-hectare unthinned 18-year rotation stand, as described before. Based on the predicted volume  and Root-to-shoot ratio (R) are strongly correlated with DBH and total height, and less strongly correlated with tree age. BEF and R decrease with DBH, height and tree age. The relationship between them suggests a negative exponential curve toward an asymptote with increasing BEF and R.• For the 2 and lowest Syx could be achieved using a combination of the following independent variables: DBH, height and age for BEF estimation; and DBH and height for R estimation;• In this study the highest R• The use of default BEF and R should be avoided due to the great possibility of obtaining spurious results. For pine plantations in southern Brazil the overestimation may be over 33%;2 removals from sinks predicted by a project that uses either default or mean BEF and R values.• Finally, caution should be used by forest offset developers since the process of verification and certification may not confirm COPinus elliottii and P. taeda individuals growing across southern Paraná State, Brazil. A direct method (weighing) was applied to obtain fresh biomass weight in the field. Belowground biomass was obtained after excavation and cleaning of the roots over 2 mm of diameter at 50 cm depth.The data used in this study came from 70 sampled The sampled trees were representative of the local conditions and previously categorized by DBH and age classes. Girth at breast height of each sample tree was measured using ordinary metric tape, and values were converted to DBH for calculations and modeling. After felling, the top bole length of each tree was measured using tape and taken to be tree total height - H. Age was determined by tree ring counting and from historic records.For the biomass weighing in the field, each tree was cut up into five biomass pools: bole, thick branches over 4 cm of diameter, thin branches under 4 cm of diameter, foliage, and roots. Biomass was determined following IPCC recommendations . Each biThe biomass expansion factor (BEF) definition used in this study is based upon FAO (1997) , i.e., twhere:BEF = biomass expansion factor (dimensionless);Wcrown = tree crown dry weight (g), composed of foliage, thick and thin branches;Wbole = tree bole dry weight (g); andWaboveround = Wcrown + Wbole (g).The root-to-shoot ratio calculations were conducted using the formula below, as indicated by the , which dwhere:R = root-to-shoot ratio (dimensionless); andWroot = tree root dry weight (g).Correlation coefficients of all variable combinations were calculated in order to understand the relationships among them and in turn to develop models to estimate BEF and R as functions of the more easily measured forest inventory variables . Twelve mathematical models were tested to estimate BEF and R from DBH, tree height and age as and presented in Table %), highest coefficient of determination adjusted to number of cases and coefficients (R2adj), and optimal performance in a graphical analysis of residuals.The best-fit model was selected in accordance with the following criteria: smallest percentage standard error of estimate  [-1, from lab determination, in accordance with IPCC nomenclature [2 equivalent (t/ha) by multiplying by the ratio 44/12 .The comparison was done by calculating COSISPINUS . Carbon . (2006)  to 0.41 nclature . Carbon The authors declare that they have no competing interests. The views expressed in this publication are those of the authors.CRS, APDC and FS conceived, drafted the manuscript and developed the methodological approaches. All authors read and approved the final manuscript.


Our objectives were to perform a longitudinal assessment of mental status in early stage Parkinson's disease (PD) patients, with brief neuropsychological tests, in order to find predictive factors for cognitive decline. Sixty-one, early stage, and nondemented patients were assessed twice, over a 2-year interval, with a global cognitive test ) and a frontal function test ) and motor function scales. Dementia and hallucinations were diagnosed according to the DSM-IV criteria. Cognitive function scores did not decrease significantly, except for FAB lexical fluency score. Four patients presented with dementia at followup. The MMSE score below cut-off, worse gait dysfunction, the nontremor motor subtype, and hallucinations were significantly related to dementia. Rigidity and speech dysfunction were related to dementia and a decrease in FAB scores. We can conclude that decline in the MMSE and FAB scores is small and heterogeneous in the early stages of PD. Scores below cut-off in the MMSE could be helpful to predict dementia. Nontremor motor deficits could be predictive factors for frontal cognitive decline and dementia. Parkinson's disease is a movement disorder, defined by a combination of tremor, rigidity, bradykinesia, and gait disturbances . Lately,Seventy-five early stage PD patients, diagnosed according to validated criteria , were cot0 and t1), with the same instruments and by the same observer. Patients were assessed twice, with a two-year interval  predominant motor groups, according to the classification system proposed by Jankovic and coworkers [Patients were assessed with the unified Parkinson's disease rating scale (UPDRS) parts II and III , after roworkers . For staoworkers .PD associated with a decreased global cognitive efficiency and also for detecting impairment in more than one cognitive domain [ Global cognitive function was evaluated with the MMSE . The MMSe domain  and has e domain , 23. Frontal function was assessed with the FAB . The froPortuguese validated versions of the tests were used , 29. We  Given that the instruments were applied by the same observer in two different time points, it is important to verify the test-retest variability of the tests and the their intrarater reliability to make sure that the changes we observe are real and not influenced by the variability of the test itself. The validity and reliability of the FAB were confirmed by several studies , 31. Tes Dementia and the presence of hallucinations were diagnosed according to the DSM-IV-R criteria . HalluciThe incidence of dementia was calculated by dividing new cases of dementia by the number of person-years at risk throughout the observation period. Because it is not possible to know the precise time a subject became demented, it was assumed to occur in the midpoint of the period of observation.t0 and t1, using paired sample t-tests or the Wilcoxon tests (depending on the distribution of the samples). Variations in FAB and MMSE scores were also calculated for each patient, as a measure of change: score at t1 − score at t0. Paired proportions  were compared by means of McNemar's tests. In a first analysis, we compared the differences in the FAB and the MMSE total and partial scores between t0 and the presence of cognitive decline at t1. Predictor variables (independent variables) were UPDRS total score, bradykinesia, rigidity, tremor, speech, gait-posture scores, Hoehn and Yahr scores, age, age of onset, diration of disease, education, gender, DED, global cognitive dysfunction, frontal cognitive dysfunction and presence of hallucinations. Outcome variables (dependent variables) were dementia at t1, change in the MMSE, and change in the FAB. To test the relation between predictor and outcome variables, the former were dichotomized at the median. Fisher's exact test was used to test the relation between predictor variables and dementia, and Mann-Whitney tests were used to test the relation between predictor variables and the MMSE and FAB change. Multivariate analysis was not performed, either because there were few positive cases (dementia) or because few variables were found as significant predictors (FAB and MMSE change).  In a second analysis, we studied the relation between cognitive tests scores and clinical variables at t-tests or chi-square tests.  In a third analysis, we aimed at evaluating clinical heterogeneity in the early stages of Parkinson's disease and its influence on cognitive decline. A two-step cluster analysis was performed, in which we entered all predictor variables. Differences between the clusters thus formed were tested by means of two-samples Patients signed informed consent forms, and the ethics committee of the institution approved the protocol.t0, 61 were reassessed at t1. Fourteen were not reassessed: 2 died from causes unrelated to PD; 1 refused reassessment; diagnosis changed in 4, which at follow-up were found not to have PD; 7 patients were out of contact and were lost for follow-up. Dropouts showed a tendency for older age and older age of onset. Frontal dysfunction was significantly more frequent in this group. There were no other significant differences in demographic, motor, or cognitive variables between patients lost for follow-up and the rest of the cohort . The patients with global cognitive impairment were the same at t0 and t1 (n = 6). The MMSE scores decreased in 23 patients , increased in 21 patients , and did not change in 17 patients. The frequency of frontal cognitive dysfunction increased from 26 to 32, but the difference did not reach significance (P = 0.201). The FAB scores decreased in 29 patients , increased in 23 patients , and did not change in 9 patients.At There were no significant variations in the MMSE total and subscores .t1)  . t0 and the occurrence of dementia. Higher speech, rigidity, gait/posture scores, and the presence of hallucinations and of the nontremor phenotype were significantly related to dementia. t0 and the changes in the MMSE and FAB scores. Frontal cognitive dysfunction and higher education were significantly related to the decreases in the MMSE scores. As chi-square analysis revealed that these two variables were significantly correlated , they were included as predictor variables in a linear regression analysis model, with the MMSE variation as an outcome variable. This showed that only frontal dysfunction had a significant influence in the MMSE variation . Higher rigidity and speech scores were significantly related to the decreases in the FAB scores . n = 35), cluster 1 (n = 26) patients presented with significantly higher HY stage (P < 0.00001), UPDRS total score (P < 0.00001) dysarthria (P < 0.00001), tremor (P = 0.019), rigidity (P = 0.004), bradykinesia (P < 0.00001), gait and postural instability (P < 0.00001) scores, and a significantly higher prevalence of the nontremor phenotype (P < 0.00001). Patients with hallucinations were all included in cluster 1 (P = 0.029). Patients in cluster 1 showed a more significant decrease in the FAB scores (P = 0.040). Patients who subsequently developed dementia were all included in cluster 1 (P = 0.029).Cluster analysis yielded two clusters. Compared to patients in cluster 2 . Incidence was lower than in most studies, in which this figure ranged from 30 to 107/1000 , 43, 44.Nontremor motor scores, nontremor motor phenotype, the presence of hallucinations, and scores below cut-off in the MMSE were related to dementia at follow-up. Significant relation between hallucinations and cognitive dysfunction in PD has been found in several studies , 47. NonPrevious work has suggested that the MMSE could be less sensitive to mild cognitive impairment, when compared to frontal oriented tests, like the Montreal cognitive assessment scale –15, althContrary to the MMSE scores, the FAB scores were not useful in predicting dementia. This could be related to the nature of cognitive deficits in PD-related dementia. Previous investigation has shown a significant relation between the progression to dementia and the superimposition of non-frontal deficits in patients with frontal deterioration . In thisNo variable was predictive of a decline in the MMSE, except for the presence of frontal dysfunction. Although our data does not allow for a straightforward explanation for these findings, we could hypothesize that, frontal dysfunction being the first step in PD-related cognitive deterioration, as mentioned above, it could act as a predictor in some patients of widespread decline of cognitive function. On the other hand, some studies , 25 haveSimilar to dementia, frontal dysfunction was predicted by nontremor motor symptoms, although the pattern was slightly different. In particular, patients with higher gait and postural dysfunction scores at baseline did not present a greater decline in the FAB scores. As previously discussed, gait dysfunction seems to be mostly correlated to cholinergic rather than to dopaminergic deficits. Other authors found an association between executive dysfunction and dopamine responsive symptoms, while cortical posterior deficits were associated with dopamine resistant symptoms . William Cluster analysis showed two groups that differed regarding the presence of hallucinations and the severity of nontremor motor symptoms. The cluster with worse nontremor symptoms and hallucinations showed a steeper progression of frontal dysfunction and a higher prevalence of dementia, which is in accordance with results from the previous analysis. Comparison with other studies is difficult, because cluster analysis depends on the variables that are included. However, Erro and collaborators  did findThe present study has several limitations, which should be taken into account when discussing the data. Because we assessed an early stage cohort, and the follow-up time was relatively short, the ratio of dementia conversation was very low. This prevents multivariate analysis procedures, weakens the statistical analysis, and precludes definite conclusions regarding the predictive factors for dementia in this group. Patients were recruited from a tertiary centre outpatient clinic, and the sample was small, precluding the generalization of results to an epidemiological level—it does, however, mirror the clinical experience of a Portuguese neurological center and could be informative in that context. In conclusion, our data suggests that nontremor motor deficits are predictive factors for dementia and frontal type decline in the early stages of Parkinson's disease. They also suggest that mini-mental state examination cut-off scores could be useful for predicting dementia in these stages.


To evaluate the prevalence of periodontal disease (PD) among Brazilian low-risk pregnant women and its association with sociodemographic factors, habits and oral hygiene.This cross-sectional study included 334 low-risk pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. Independent variables were: age, race/color, schooling, marital status, parity, gestational age, smoking habit, alcohol and drugs consumption, use of medication, presence of any systemic diseases and BMI (body mass index). Statistical analyses provided prevalence ratios and their respective 95%CI and also a multivariate analysis.adj 2.01, 95%CI 1.41 - 2.88). Poor oral hygiene was associated with PD by the mean values of plaque and bleeding on probing indexes significantly greater in PD group.The prevalence of PD was 47% and significantly associated with higher gestational age , maternal age 25-29 years, obesity  and the presence of gingival bleeding on probing (ORThe prevalence of PD is high and associated with gingival bleeding on probing, more advanced gestational age and obesity. A program of oral health care should be included in prenatal care for early pregnancy, especially for low-income populations. Periodontal disease is a common oral infection with prevalence ranging from 10-60%, and refers to gingivitis and periodontitis . PD invoFactors including the host's systemic status should be studied since they may affect the prevalence, progression and severity of PD. Sex hormones have been indicated as important modifying factors that may influence the pathogenesis of PD .During pregnancy, progesterone levels increase 10-fold and estrogen levels 30-fold compared to those observed on menstrual cycle due to their continuous production. Physiological changes in metabolism include oral microbial species, immune response and cell metabolism. The increase in progesterone results in greater vascular permeability, gingival edema, crevicular fluid levels and prostaglandin production, which may lead to gingival inflammation . In addiThen, in fact there is a relationship between pregnancy and periodontal status -11. StudBased on clinical observations, the prevalence of PD during pregnancy varies from 35% in some studies to 100% in others ,19. ThisRecent scientific publications concentrate on a different aspect of the consequences of the increased PD rates during pregnancy. They focused on preventing exacerbation of periodontal conditions and possible treatment, not only because the disease could interfere with systemic health but also as a way to improve oral health status. There is still limited information about the periodontal conditions of Brazilian pregnant women and more representative epidemiologic studies are necessary. Therefore, the objective of this study was to evaluate the periodontal status of a sample of Brazilian low-income and low-risk pregnant women, assessing the full-mouth prevalence, extent and severity of clinical attachment loss, besides the other clinical parameters, to measure the prevalence of PD and to investigate its possible association with some sociodemographic factors, habits and oral hygiene.This is a cross-sectional study that assesses the results of a periodontal evaluation, the prevalence of PD and its association with sociodemographic factors, habits and oral hygiene, performed with low-income and low-risk pregnant women  receiving prenatal care at the maternity of the University of Campinas, Brazil, who voluntarily agreed to participate in the study after signing an informed consent form. The study was approved by the Institutional Review Board.Each one of 334 pregnant women, aged 18 to 42, underwent a single periodontal examination on the day of a scheduled prenatal visit, between February 2004 and August 2005.Inclusion criteria were: gestational age ≤ 32 weeks and low risk. Women carrying twins, with a greater risk of preterm and/or low birth-weight , with a previous preterm and with two or more Caesarean sections were excluded from the study.Women attending the prenatal outpatient clinic were interviewed by a nurse during the educational support group meetings. The nurse briefly explained the objectives of the study and the procedures involved. Then they were referred directly to the odontological clinic to receive additional information and sign the informed consent form. Immediately afterwards, a questionnaire was filled out for collecting socio-demographic and habits variables, gestational age, and the periodontal examination was done.It was carried out once during pregnancy before 32 weeks of gestation. The data were recorded on a clinical record form with a complete clinical and periodontal description of all the teeth including third molars. Oral hygiene status was assessed as the percentage of surfaces with plaque, by the dichotomous plaque index (presence or absence of plaque) (PI) . ProbingThe presence of 4 or more teeth showing at least one site with 4 mm of PPD and clinical attachment loss at the same site, with BOP, was diagnosed as periodontal disease (PD). These criteria were operationally selected for the clinical definition of pregnant women who positively and unequivocally exhibited PD specifically for this study. Therefore two groups of pregnant women were then defined with the purpose to associate them with the socio-demographic and habit variables: one with PD and other without PD. In order to conduct a more accurate evaluation of the characteristics of PD in this population, the extension of the disease was also classified as follows: P1: at least four teeth with PPD and CAL of 4-6 mm; P2: at least four teeth with PPD and CAL of 7-9 mm; and P3: at least four teeth with PPD and CAL of 10 mm. Among the women classified as without PD, those that had BOP in more than 25% of sites were classified as having only gingivitis in some sites, and when it was ≤ 25%, they were classified as having healthy periodontal status .Information was collected from the pregnant women's files and at the time of the exam, by means of a questionnaire, in order to identify the predictor/independent variables that could be associated with PD in this population. These variables were: socio-demographic variables , habit variables , gestational age at examination (weeks), besides some self-reported oral variables.2 test was used to measure statistical significance. Prevalence ratios (PR with their respective 95% CI) were estimated for the different categories of each possible variable evaluated. Student's parametric t-test was used to compare BOP and PI. Next, a multiple logistic regression analysis was carried out that included PD as the outcome and all others as independent variables. The level of significance was established at 5% and Epi.Info 6.1 and SAS were used for the statistical analysis procedures.When each case was finished, with the information on periodontal examination and socio-demographic and habits factors, the form was checked for completeness and correctness. The information was entered to feed a computer database specifically prepared for this study. Consistency tests were then performed to identify errors with are corrected after checking the correspondent information in the clinical records. For the analyses, the frequency distribution of variables was initially evaluated in the two groups and the χA total of 334 pregnant women were included in the study. Among these, 157 were classified as with PD, and 177 without PD, what represents a 47% prevalence of exposure of PD in this population Table , the onlAmong all the "self-reported" periodontal variables studied, the reference to gingival bleeding was statistically associated with approximately a two-fold increased risk in prevalence of PD, while not using dental floss was associated with a 1.32-times greater risk Table . In the There were 157 diagnosed cases with PD, the majority of them  with 4-6 mm of attachment loss. Of the 334 women evaluated, all were found to have any gingival BOP at any site, in both groups, with or without PD. Nine women (2.7%) were found to have a BOP index ≤ 25%, while 325 cases (97.3%) had an index > 25%. Among the 177 women classified as without PD in this study (53%), only 16 women (4.8%) had no periodontal attachment loss at all; among these, 9 cases were found to have a BOP index > 25%, gingivitis, while 7 cases (2.1%) had this index ≤ 25%; 161 women (48.2%) had some attachment loss < 4 mm at some site. These results show that only 2.1% of the entire sample of pregnant women in this study had a real oral health status, without any attachment loss at any site or gingivitis (bleeding on probing index ≤ 25%) (data not shown in table).et al. [et al. [The current study found a high prevalence of PD during pregnancy of 47% showing a poor periodontal condition of this low-income Brazilian pregnant women sample. Other South American study  reportedet al.  and Lief [et al. , who fou [et al. .et al. [More cases of periodontal damage were detected when the examination was performed later in gestation. These findings are in agreement with data in the literature showing an exacerbation in pre-existing periodontal status as pregnancy progresses ,11,20. Tet al.  found gret al. [et al. [et al. [Some studies in which more than one examination was performed during pregnancy showed no clinical attachment loss during the interim period. Tilakaratne et al.  reported [et al.  followed [et al.  comparedet al. [Two recent studies found positive results with respect to clinical attachment loss during pregnancy. Although the increase in PPD may represent reversible changes previously documented in pregnant women , increaset al.  reportedA significant association was found between obesity (BMI > 29) and PD. Although this has not been a focus of other studies on PD in pregnancy, our results are in agreement with those from other studies in non-pregnant populations, whom reported a higher risk of obese subjects having periodontitis ,26. BMI et al. [28. The low-income seems to be an important factor associated with poor oral health in Brazilian studied subpopulations [Self-reported gingival bleeding was statistically associated with an approximately two-fold risk of having PD; while the non-use of dental floss was associated with a 1.32-fold risk. These findings are in agreement with the greatest mean values found for the BOP and plaque indexes in the group with PD. Sarlati et al.  also shoulations , witch pulations .Young low-income pregnant women of this sample, with age between 25 and 29 years old, showed association with PD, reflecting a social health oral concern, considering its progression if not treated . The horIn the multiple logistic regression analysis, the only independent variable that proved to be statistically associated with the prevalence of PD during pregnancy was the presence of gingival BOP. This finding is in agreement with data reported in the literature that gingival BOP is the most consistent factor found during active progression of the PD and that it may be a predictor of future clinical attachment loss, mainly when associated with greater PPD -34.Even if new periodontal pockets appear and revert after pregnancy , it is iA program of oral health care should be developed and implemented for early pregnancy, especially for low-income populations. It should provide information on oral hygiene and periodontal treatment during prenatal care, particularly among women at greater risk. If this is true for low risk pregnant women we could probably assume that it would also be the case for high risk pregnancy as well. Although a study published in the literature has reported a reduction in gingival inflammation occurring three months following delivery , oral heBMI: body mass index; BOP: Bleeding on probing; CAL: clinical attachment level; GR: gingival recession; PD: periodontal disease; PI: plaque index; PPD: Probing pocket depth; PR: prevalence ratio.MV, AWS and JGC participated in all steps of the study, including research planning, data collection, analysis and writing the manuscripts. SSM performed the statistical analysis. All authors gave suggestions, read the manuscript carefully, fully agreed on its content and approved its final version.The authors declare that they have no competing interests.


Although the outcomes of caustic ingestion differ between children and adults, it is unclear whether such outcomes differ among adults as a function of their age. This retrospective study was performed to ascertain whether the clinical outcomes of caustic ingestion differ significantly between elderly and non-elderly adults.Medical records of patients hospitalized for caustic ingestion between June 1999 and July 2009 were reviewed retrospectively. Three hundred eighty nine patients between the ages of 17 and 107 years were divided into two groups: non-elderly (< 65 years) and elderly (≥ 65 years). Mucosal damage was graded using esophagogastroduodenoscopy (EGD). Parameters examined in this study included gender, intent of ingestion, substance ingested, systemic and gastrointestinal complications, psychological and systemic comorbidities, severity of mucosal injury, and time to expiration.The incidence of psychological comorbidities was higher for the non-elderly group. By contrast, the incidence of systemic comorbidities, the grade of severity of mucosal damage, and the incidence of systemic complications were higher for the elderly group. The percentages of ICU admissions and deaths in the ICU were higher and the cumulative survival rate was lower for the elderly group. Elderly subjects, those with systemic complications had the greatest mortality risk due to caustic ingestion.Caustic ingestion by subjects ≥65 years of age is associated with poorer clinical outcomes as compared to subjects < 65 years of age; elderly subjects with systemic complications have the poorest clinical outcomes. The severity of gastrointestinal tract injury appears to have no impact on the survival of elderly subjects. Caustic agents are known to provoke a wide range of gastrointestinal (GI) tract injuries with long-term complications; such complications include esophageal stricture and the development of esophageal carcinoma . EsophagCaustic agents with pH values < 2 or > 12 are extremely corrosive to the GI tract. The extent of tissue destruction by such agents is dependent on multiple variables such as type, physical form, and concentration . In the Caustic ingestion in children is primarily accidental and is observed most commonly in children less than 6 years of age . In adulThe clinical outcomes of caustic ingestion are assumed to be more serious for elderly as opposed to non-elderly subjects but such outcomes are only rarely investigated. The present study was undertaken to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of ingestion, substance ingested, systemic and GI complications, severity of mucosal injury, and time to expiration.Informed written consent was obtained from all subjects in this study, which was performed according to the guidelines of our institutional review board (IRB). Approval for this retrospective study (CGMH98-3352B) was obtained from our IRB.The medical records from 389 patients (ranging in age from 17 to 107 years) who were admitted to the Department of Gastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, for caustic ingestion between June 1999 and July 2009 were reviewed. Patients were admitted to the Department of Gastroenterology from the Emergency Room (ER). EGD with a standard upper GI endoscope was performed on all patients within 24 h of ingestion by physicians experienced with this technique. The endoscopes used in this study were the Olympus GIF XQ-230, the GIF Q 240X, and the GIF Q-260; the diameters of these endoscopes are 9.2, 9.4, and 9.2 mm, respectively . Extreme care was used when passing the endoscope through the injured segment. If perforation was suspected, the procedure was stopped immediately and the endoscope withdrawn.Subjects were divided into two groups according to age: the non-elderly (< 65 years) and elderly (≥65 years) groups. The parameters investigated in these two groups included gender, intent of ingestion, substance ingested, systemic and GI complications, psychological and systemic comorbidities, severity of mucosal injury as assessed by EGD, and time to expiration. Systemic complications included liver damage, renal insufficiency, disseminated intravascular coagulation (DIC), and hemolysis. Liver damage was defined as a three-fold elevation in the concentration of serum alanine aminotransferase or aspartate aminotransferase above the upper limit of normal. Renal insufficiency was defined as a plasma creatinine concentration greater than 1.4 mg/dL in the absence of other renal diseases. Criteria for DIC were prolonged plasma coagulation time, decreased fibrinogen or antithrombin values, and decreased platelet count. Upper GI complications included bleeding, perforation, and stricture formation. Bleeding was defined as melena, hematemesis, and/or coffee ground vomitus. Perforation was diagnosed by the presence of free air on a plain chest radiograph. Stricture was defined as dysphagia, symptoms of regurgitation, or difficulty in swallowing with confirmation by endoscopy, esophagogram, and/or upper GI radiography.et al. [Mucosal damage was graded according to the modified endoscopic classification of Zargar et al.  as follo+, and K+ were performed in the ER. Based on the judgment of the ER physician in charge, patients were treated with a proton pump inhibitor, H2 antagonist, or sucralfate gel. Oral intake was withheld and parenteral nutrition was provided until evidence was obtained that the condition of the patient had stabilized. Antibiotics were not administered routinely due to national healthcare insurance restrictions. If infection was suspected, empirical antimicrobial therapies  were administered until blood cultures were obtained. If a pulmonary or respiratory complication was suspected, a chest X-ray was performed. Aspiration pneumonia was defined as a lung infection developing after accidental inhalation of foods, liquids, or stomach contents and was diagnosed by chest X-ray; patient history served to confirm that no other form of lung disease was present.Blood tests, including complete blood and differential counts, and measurements of alanine transaminase, creatinine, NaIf the patient's condition became unstable or respiratory difficulty was encountered, he/she was transferred to the intensive care unit (ICU) for further evaluation. After discharge, each surviving patient was followed at the outpatient clinic for at least 1 month. If the patient had symptoms of dysphagia during follow-up, an upper GI series or EGD was performed to confirm the presence of stricture. Patients with GI or systemic complications were followed until these patients expired. Those with persistent dilatation were followed for over 7 years. The overall range of follow-up times, therefore, was 3 days to more than 7 years.n with a percentage (%), with the exception of age which is expressed as the median (Q1-Q3) and as the mean (minimum-maximum). Pearson chi-square or Fisher's exact tests were performed to identify dispersions in the demographics and clinical findings among the two age groups. For time-related data, Kaplan-Meier analysis with a log-rank test was also performed to indicate the cumulative survival rate by age. Furthermore, univariate and multivariate Cox proportional hazard ratio regression models were used to obtain the hazard rate (HR) with a 95% confidence interval and to determine the cumulative survival rate as a function of age and other confounders. Based on the proportion of systemic complications and the Type I error probability associated with these models, the null hypothesis is 0.05 and the observed power is equal to 98.6%. All statistical assessments were considered significant at a P value of less than 0.05. Statistical analyses were performed using SPSS 15.0 statistics software .Demographic and clinical findings are presented as Three hundred eighty nine subjects were enrolled. The non-elderly group was comprised of 321 (82.5%) subjects less than 65 years of age, and the elderly group was comprised of 68 (17.5%) subjects 65 years of age or older. Median and mean ages for all subjects and for the non-elderly and elderly groups are presented in Table P = 0.016). Additionally, the severity of mucosal damage was found to be greater for subjects in the elderly group . This difference in severity was primarily attributable to the difference between the two groups in the number of subjects with a mucosal damage grade of 3b (P < 0.001).Demographic characteristics of the two groups are also presented in Table P = 0.009). As expected, the incidence of systemic comorbidity was higher for the elderly (73.5%) as compared to the non-elderly  group.Table The incidences of suicide attempts and accidental ingestions were similar for the two groups, with suicide attempts more commonly involved.P < 0.001). The differences in incidences of aspiration pneumonia, respiratory failure, and DIC between the two groups were statistically significant . By contrast, the incidence of hepatic complications did not differ between the two groups (P = 0.719). Fever developed in 21.1% of all subjects, in 17.8% of those in the non-elderly group, and in 36.6% of those in the elderly group; the difference between the two groups was significant (P = 0.001).Systemic complications included aspiration pneumonia, respiratory failure, DIC, and hepatic complications. The overall incidence of these complications was higher in the elderly than in the non-elderly group .Treatments were selected according to the complication manifested and the experience of the treating physician(s). These procedures included the most appropriate surgery and/or dilatation and administration of antibiotics. Surgical procedures included feeding jejunostomy, subtotal gastrectomy, esophagectomy, esophageal reconstruction, and the Whipple operation for perforation. If a stricture formed, patients received dilatation or/and surgery. In the event that bleeding occurred, EGD was repeated if possible; some patients died suddenly following hematemesis. If the event of perforation, a surgeon was consulted immediately; some patients expired suddenly after diagnosis by an imaging technique such as chest X-ray. The incidences of surgical treatments and of dilatation did not differ significantly between the two groups. If infection was suspected, empirical antimicrobial therapy was administered immediately. More specific therapy was administered when the infectious organism was identified. Antibiotics were administered to 29.3% of all subjects, to 25.2% of those in the non-elderly group, and to 48.5% of those in the elderly group; the difference between the two groups was significant (P < 0.001). Furthermore, the percentage of patients who expired following admission to the ICU was greater for the elderly group than for the non-elderly group . However, no differences between the two groups regarding days in the ICU or time to expiration in the ICU were observed. Causes of mortality for the non-elderly group were: DIC (3 cases), hemotypsis (4 cases), tracheal perforation (1 case), and respiratory failure (4 cases). Causes of mortality for the elderly group were: DIC (2 cases), hemotypsis (1 case), perforation (1 case), and respiratory failure (8 cases).Admission to the ICU was required for 29.4% of patients in the elderly group as compared to 8.1% of patients in the non-elderly group; the difference in admissions was significant (P < 0.001). Apart from age, other variables correlating with increased mortality risk based on univariate analysis in order of decreasing HR were: systemic complications , antibiotic usage , fever , intended suicide , GI complications , hepatic complications , respiratory failure , grade 2a/2b injury  and grade 3a injury . The HR for grade 1 injury was 0 because no patients in this category expired.Table The age-related clinical confounders shown in Table P < 0.001).Figure P value of < 0.001 from the log-rank test; Figure P < 0.001; Table The present study is the first to demonstrate that the clinical outcome for adults who ingest caustic substances is related to age (P = 0.003).Aspiration pneumonia is part of a spectrum of inflammatory pulmonary disorders which can increase morbidity and mortality even in anesthetized patients . CausticIn contrast to the increased mortality risk associated with the presence of systemic complications in the elderly group, the severity of GI tract injury appears to have had no impact on survival despite the fact that patients in this group had more severe mucosal injury (grade 3b) than those in the younger group. Upper GI tract bleeding after caustic injury is another major complication of caustic ingestion. In the present study, the bleeder rate was approximately 4.4% for all patients, regardless of age. In addition, the incidence of other GI complications such as stricture, perforation and fistula formation was also independent of age. Furthermore, based on the multivariate Cox-regression model of mortality risk considering relative age-related confounding factors, neither the type of GI complication nor the location or severity of GI tract injury appears to have an impact on survival after caustic injury in the elderly.P < 0.001). In addition, no differences were observed between the two age groups regarding the type of ingested substance, the pH of the ingested substance, or the site most severely damaged by the caustic agent.Certain findings of the present study are not unexpected. For example, the incidence of comorbidities such as diabetes mellitus, hypertension, major organ disease or operative history was higher for elderly subjects . This observation strongly supports the proposal that complications of the ingestion were consequences of the ingestion itself as opposed to consequences of comorbidities. It should be noted, however, that the percentage of suicide attempts in this study was higher than that reported in other studies [The percentage of all patients in the present study who attempted suicide was greater than 70%; similar percentages were obtained in each of the two age groups (72.9% for the non-elderly group and 70.6% for the elderly group; Certain limitations of the present study should also be noted. Firstly, this retrospective review involved a limited number of patients in a community hospital setting. Secondly, the clinical outcomes for subjects who attempted suicide and for those who suffered grade 3b injuries were not specifically provided. Future prospective studies should focus on greater numbers of patients and include a broader range of patient settings with special emphasis on factors such as type of GI complication, location of GI injury, grade and type of GI injury, comorbidities, intent of caustic ingestion, and incidence of aspiration pneumonia.In conclusion, the clinical outcome for adults who ingest caustic substances is age-related. The incidence of systemic complications, including respiratory failure, aspiration pneumonia, and DIC, is higher in elderly as opposed to non-elderly adults following caustic ingestion; the incidence of systemic complications in these elderly subjects correlates with their mortality risk. The severity of GI tract injury does not appear to impact the survival of elderly subjects. When the elderly suffer from caustic injury, their respiratory systems must be supported with particular care to prevent aspiration pneumonia. If infection is suspected, prophylactic administration of antibiotics is indicated and should be done as soon as possible.The authors declare that they have no competing interests.JMC, LYH and HTC participated in drafting of the manuscript. NJL and HTC participated in conception and design. CJP and MHT participated in analysis and interpretation of data. CSL and YYC participated in critical revision of the manuscript for important intellectual content. CCL, CTU and HTC approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/11/72/prepub