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Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction.We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction.Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period.SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs.None.For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Highlights • Dynamic transmission models of infectious disease capture the herd immunity effects of vaccination. • We compared dynamic and static models of maternal acellular pertussis (aP) immunization built with Brazilian data. • At infant vaccine coverage 90–95%. • The background effect of routine infant vaccination is critical to the cost-effectiveness of maternal aP immunization., Background This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. Methods We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models’ different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. Results The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90–95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models’ estimates over their different time horizons are compared at infant coverage

Background Pertussis is associated with significant disease burden in children worldwide. In addition to its cyclical nature, resurgences of pertussis cases, hospitalizations and deaths have been reported by many countries. We describe the dynamics of pertussis in Brazil, a middle-income country that has experienced a resurgence and that provides good quality data to allow building a dynamic transmission disease model. Methods We conducted a descriptive analysis of pertussis burden considering data from the national disease surveillance system, national hospitalization information system and national mortality registry. Study period was 2000–2016. Absolute numbers and rates per 100,000 inhabitants over time, by age sub-groups and geographical regions are presented. Results From 2000 to 2016, a total of 37,299 reported pertussis cases, 25,240 hospitalizations, and 601 deaths due to pertussis were reported. Although the outcomes – pertussis cases, hospitalizations, and deaths – come from independent information systems, our results document low disease burden with periodic increases every 3–4 years during the years 2000–2010, followed by a sharp increase which peaked in 2014. In both periods, disease burden is concentrated in young children, while its more serious outcomes – hospitalizations and deaths, are concentrated in infants. Pre-outbreak and outbreak disease burden as well as timing of peak during the outbreak period vary by states and within geographical regions, representing valuable resources of data for modelling purposes. Conclusion Consistent disease burden patterns were observed over time in Brazil using a variety of data sources. Given the scarcity of good epidemiological data on pertussis available from low- and middle-income countries, our reported data provide valuable information for the assessment of the public health impact and cost-effectiveness modelling studies of newer strategies to prevent and control pertussis. These data were used to build and calibrate a national dynamic transmission model, which was used to evaluate the cost-effectiveness of maternal immunization. Clinical Trial registry name and registration number: Not applicable.

Patients undergoing coronary angiography after myocardial infarction (MI) often develop cardiac and renal dysfunction. We hypothesized that the apolipoprotein A-I mimetic peptide 4F (4F) would prevent those complications. Male Wistar rats were fed a high-cholesterol diet for 8 days. The rats were then anesthetized with isoflurane and randomly divided into five groups: a control group (sham-operated rats), and four groups of rats induced to MI by left coronary artery ligation, the rats in three of those groups being injected 6 h later, with the nonionic contrast agent iopamidol, 4F, and iopamidol plus 4F, respectively. At postprocedure hour 24, we performed the following experiments/tests ( n = 8 rats/group): metabolic cage studies; creatinine clearance studies; analysis of creatinine, urea, sodium, potassium, triglycerides, total cholesterol, very low-, low- and high-density lipoproteins (VLDL, LDL, and HDL); immunohistochemistry; histomorphometry; Western blot analysis; and transmission electron microscopy. In another set of experiments ( n = 8 rats/group), also performed at postprocedure hour 24, we measured mean arterial pressure, heart rate, heart rate variability, echocardiographic parameters, left ventricular systolic pressure, and left ventricular end-diastolic pressure. 4F protected against MI-induced increases in total cholesterol, triglycerides, and LDL; increased HDL levels; reversed autonomic and cardiac dysfunction; decreased the myocardial ischemic area; minimized renal and cardiac apoptosis; protected mitochondria; and strengthened endothelia possibly by minimizing Toll-like receptor 4 upregulation (thus restoring endothelial nitric oxide synthase protein expression) and by upregulating vascular endothelial growth factor protein expression. 4F-treated animals showed signs of cardiac neovascularization. The nitric oxide-dependent cardioprotection and renoprotection provided by 4F could have implications for post-MI treatment.

Background Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. Methods This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV − AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. Results Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV − AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25–0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV − AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18–0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99–4.68). Conclusions In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Clinical Background: Although chronic kidney disease (CKD) and smoking are both associated with high rates of morbidity and mortality, the interplay between the two is not widely understood. Epidemiology: The incidence of CKD progression has been shown to be significantly higher among current and former smokers, and continued smoking thereafter has been associated with a nearly twofold higher risk of death. Challenges: Because it is a silent disease, CKD is often diagnosed in advanced stages, which underscores the importance of targeted, active screening for CKD. When CKD progresses to stage 5, life expectancy is drastically shortened unless life-saving renal replacement therapy (dialysis or kidney transplantation) is initiated. The treatment of smoking, which is a risk factor for CKD, also poses a challenge. Less than 10% of adults who want to quit smoking succeed in doing so, and those who do quit typically succeed only after making multiple attempts. In addition, many smokers have limited access to smoking cessation services, are unaware of available resources, or have misconceptions about smoking cessation therapies. Prevention and Treatment: There is evidence that quitting smoking may help prevent the development of CKD. However, glomerular filtration rates have been found to be higher in smokers than in nonsmokers, which could confound efforts to recognize smoking as a major risk factor for kidney disease. Efforts should continue to focus on the prevention of smoking, and nephrologists should promote smoking cessation as a means to prevent CKD progression.

AUTHOR CONTRIBUTIONS Arantes MF was responsible for the editorial idea and conception, manuscript drafting and final approval of the version to be published.Rodrigues CE, Seabra VF, Seabra VF, Reichert BV, Sales GTM, Smolentzov I and Cabrera CPS were responsible for critical review of the manuscript, intellectual content, and final approval of the version to be published. Andrade L was responsible for mentoring, critical review, and final approval of the version to be published. […] Renal involvement in patients with COVID-19

Introdução: A nutrição adequada pode reduzir as complicações, o tempo de internação hospitalar e melhorar os desfechos clínicos dos pacientes. Objetivo: Avaliar a adequação da prescrição proteica na terapia nutricional enteral para pacientes oncológicos e comparar a prescrição nutricional proteica com as recomendações específicas disponíveis para oncologia, segundo a literatura atual. Método: Trata-se de um estudo quantitativo retrospectivo. Os dados da pesquisa foram obtidos por meio do mapa de uso diário pela nutricionista. Resultados: 54% dos pacientes eram mulheres, 41% das mulheres tinham câncer de mama e 21% dos homens, câncer de pulmão. Pelo NRS 2002, o escore de risco nutricional 3 foi prevalente em adultos e idosos de ambos os sexos. Adultos eutróficos representaram 64% e idosos desnutridos, 50%. A exigência proteica média para adultos eutróficos foi de 1,5 g ptn/kg; para desnutridos, 2,1 g ptn/kg; para sobrepeso, 1,4 g ptn/kg; e para o obesos, 1,8 g ptn/kg. Para a desnutrição em idosos, a exigência proteica média foi de 1,4 g ptn/kg; para eutróficos, 1,5 g ptn/kg; e para obesos, 1,5 g ptn/kg. Nenhum resultado avaliado apresentou significância estatística. Conclusão: A malignidade da doença de base, a idade e a presença do risco nutricional sugerem maior necessidade de incrementar o quantitativo de aporte nutricional. Evidencia-se também a necessidade da utilização de módulos de proteína para adequar a prescrição nutricional principalmente aos pacientes obesos.

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6 months, with a booster at 12–15 months of age. The meningococcal C conjugate vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with a booster dose at 12–15 months of age and no catch-up for older age groups. In this interrupted time-series analysis study, we used Brazilian mortality data from 2005 to 2015 for children under five years of age (excluding data from the state of Bahia) to assess the combined impact of these vaccines on the overall burden of meningitis mortality among children aged 0–23 months and 2–4 years, as defined using meningitis and meningococcemia specific International Classification of Diseases - tenth revision codes. Secular trends and seasonality were taken into account. We found significant reductions for both age groups relative to those observed for the comparison group of diseases, with immediate effects after the transition period (2010-2011) of 29.2% and 27.5% for children aged 0–23 months and 2–4 years, respectively. These immediate effects were sustained throughout the post-vaccination period (2012–2015). In total, 337 deaths were averted by the combined effect of both vaccines, 238 (95%CI 169-319) for children aged 0–23 months and 99 (95%CI 56–144) for those aged 2–4 years. These results add strong evidence in support of investments in these vaccines by low and middle-income countries.

Objective To determine and compare hospitalization costs of bacterial community-acquired pneumonia cases via different costing methods under the Brazilian Public Unified Health System perspective. Methods Cost-of-illness study based on primary data collected from a sample of 59 children aged between 28 days and 35 months and hospitalized due to bacterial pneumonia. Direct medical and non-medical costs were considered and three costing methods employed: micro-costing based on medical record review, micro-costing based on therapeutic guidelines and gross-costing based on the Brazilian Public Unified Health System reimbursement rates. Costs estimates obtained via different methods were compared using the Friedman test. Results Cost estimates of inpatient cases of severe pneumonia amounted to R$ 780,70/$Int. 858.7 (medical record review), R$ 641,90/$Int. 706.90 (therapeutic guidelines) and R$ 594,80/$Int. 654.28 (Brazilian Public Unified Health System reimbursement rates). Costs estimated via micro-costing (medical record review or therapeutic guidelines) did not differ significantly (p=0.405), while estimates based on reimbursement rates were significantly lower compared to estimates based on therapeutic guidelines (p

Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013.The carriage survey was conducted among 531 children, aged 12 months to24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only.No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8-1.8%) and 95.5% (19.8-0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6-44.8%) and 185% (19.6-55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2-0.6%, p 0.001) and increase in serotype 19A (1.8-6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC ≥ 2.0 mg/L) and cefotaxime (MIC ≥ 1.0 mg/L) values.After 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.

Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP- Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP- Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-κB activation. It is noteworthy that CLP- Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprusside, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction, Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.

We aimed to investigate the nasopharyngeal colonization (NPC) by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in the elderly population and to assess the demographic factors associated with NPC. This was an observational cohort study in which outpatients aged ≥60 years were enrolled from April to August 2017, with a follow-up visit from September through December 2017. Nasopharyngeal (NP) swabs were collected, bacteria were detected and isolated, and isolates were subjected to phenotypic and molecular characterization using standard microbiological techniques. At enrolment, the rates of S. aureus, methicillin-resistant S. aureus (MRSA), H. influenzae, and S. pneumoniae among 776 elderly outpatients were 15.9%, 2.3%, 2.5%, and 2.2%, respectively. Toxin production was detected in 21.1% of methicillin-susceptible S. aureus, and three SCCmec types were identified: II/IIb, IVa, and VI. At the follow-up visit, all carriage rates were similar (p > 0.05) to the rates at enrolment. Most of S. pneumoniae serotypes were not included in pneumococcal conjugate vaccines (PCVs), except for 7F, 3, and 19A. All strains of H. influenzae were non-typeable. Previous use of antibiotics and 23-valent pneumococcal polysaccharide vaccination (p < 0.05) were risk factors for S. aureus and MRSA carriage; S. aureus colonization was also associated with chronic kidney disease (p = 0.021). S. pneumoniae carriage was associated with male gender (p = 0.032) and an absence of diabetes (p = 0.034), while not receiving an influenza vaccine (p = 0.049) and chronic obstructive pulmonary disease (p = 0.031) were risk factors for H. influenzae colonization. The frailty of study participants was not associated with colonization status. We found a higher S. aureus carriage rate compared with the S. pneumoniae- and H. influenzae-carriage rates in a well-attended population in a geriatric outpatient clinic. This is one of the few studies conducted in Brazil that can support future colonization studies among elderly individuals.

Background Little is known about clinical characteristics and management of severe yellow fever as previous yellow fever epidemics often occurred in times or areas with little access to intensive care units (ICU). We aim to describe the clinical characteristics of severe yellow fever cases requiring admission to the ICU during the 2018 yellow fever outbreak in São Paulo, Brazil. Furthermore, we report on preliminary lessons learnt regarding clinical management of severe yellow fever. Methods Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated. Results From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to the ICU in a tertiary hospital in Sao Paolo because of rapid clinical deterioration. On admission, the median AST was 7,000 IU/L, ALT 3,936 IU/L, total bilirubin 5.3 ml/dL, platelet 74 × 103/mm3, INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. The in-hospital fatality rate was 67%. Patients with diabetes mellitus had a higher case fatality rate (CFR) of 80%, while patients without diabetes had a CFR of 65%. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multi-organ failure. Conclusions Severe yellow fever is associated with a high CFR. The following management lessons were learnt: Anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels >70 μmol/L was commenced which reduced the frequency of seizures from 28% to 17%. Other new therapy strategies included early institution of plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors should be administered.

The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 × 106 WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor κB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. Significance Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate.

Predictive equations (PEs) are used for estimating resting energy expenditure (REE) when the measurements obtained from indirect calorimetry (IC) are not available. This study evaluated the degree of agreement and the accuracy between the REE measured by IC (REE-IC) and REE estimated by PE (REE-PE) in mechanically ventilated elderly patients admitted to the intensive care unit (ICU).REE-IC of 97 critically ill elderly patients was compared with REE-PE by 6 PEs: Harris and Benedict (HB) multiplied by the correction factor of 1.2; European Society for Clinical Nutrition and Metabolism (ESPEN) using the minimum (ESPENmi), average (ESPENme), and maximum (ESPENma) values; Mifflin-St Jeor; Ireton-Jones (IJ); Fredrix; and Lührmann. Degree of agreement between REE-PE and REE-IC was analyzed by the interclass correlation coefficient and the Bland-Altman test. The accuracy was calculated by the percentage of male and/or female patients whose REE-PE values differ by up to ±10% in relation to REE-IC.For both sexes, there was no difference for average REE-IC in kcal/kg when the values obtained with REE-PE by corrected HB and ESPENme were compared. A high level of agreement was demonstrated by corrected HB for both sexes, with greater accuracy for women. The best accuracy in the male group was obtained with the IJ equation but with a low level of agreement.The effectiveness of PEs is limited for estimating REE of critically ill elderly patients. Nonetheless, HB multiplied by a correction factor of 1.2 can be used until a specific PE for this group of patients is developed.

To describe long-term mortality and hospital readmissions of patients admitted to Brazilian intensive care units (ICU). Retrospective cohort study of adult patients admitted to Brazilian hospitals affiliated to the Public Healthcare System from 10 state capitals. ICU patients were paired to non-ICU patients by frequency matching (ratio 1:2), according to postal code and admission semester. Hospitalization records were linked through deterministic linkage to national mortality data. Primary outcome was mortality up to 1 year. Other outcomes were mortality and readmissions at 30 and 90 days and 3 years. Multiple Cox regressions were used adjusting for age, sex, cancer diagnosis, type of hospital, and surgical status. We included 324,594 patients (108,302 ICU and 216,292 non-ICU). ICU patients had increased hospital length of stay [9 (5–17) vs. 3 (1–6) days, p

Made available in DSpace on 2022-04-29T08:45:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-25 American Laryngological Association GlaxoSmithKline Pfizer Background: Varicella vaccine was introduced into the Brazilian Immunization Program in October 2013, as a single-dose schedule administered at 15 months of age. Its effectiveness had not yet been assessed in the country. Methods: A matched case-control study was carried out in São Paulo and Goiânia (Southeast and Midwest regions, respectively), Brazil. Suspected cases, were identified through a prospective surveillance established in the study sites. All cases had specimens from skin lesion collected for molecular laboratory testing. Cases were confirmed by either clinical or PCR of skin lesions and classified as mild, moderate, and severe disease. Two neighborhood controls were selected for each case. Cases and controls were aged 15–32 months and interviewed at home. Evidence of prior vaccination was obtained from vaccination cards. Univariate and multivariate logistic regression models were used, and odds ratio and its respective 95% confidence intervals were estimated. Vaccine effectiveness was estimated by comparing de odds of having received varicella vaccine among cases and controls. Results: A total of 168 cases and 301 controls were enrolled. Moderate and severe illness, was found in 33.3% and 9.9% of the cases. Effectiveness of a single dose varicella vaccine was 86% (95%CI 72–92%) against disease of any severity and 93% (95%CI 82–97%) against moderate and severe disease. Out of 168 cases, 81.8% had positive PCR results for wild-type strains, and 22.0% were breakthrough varicella cases. Breakthrough cases were milder compared to non-breakthrough cases (p

The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (WT) mice, klotho-haploinsufficient ( kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine- kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher α-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.

The aim of the present study was to assess the prevalence of Haemophilus influenzae type b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Few studies have reported the effect of 10-valent pneumococcal conjugate vaccine (PCV10) on otitis media (OM) in infants. In particular, no population-based study in upper-middle income countries is available. In 2010, Brazil introduced PCV10 into its routine National Immunization Program using a 3+1 schedule. We measured the impact of PCV10 on all-cause OM in children. An interrupted time-series analysis was conducted in Goiânia/Brazil considering monthly rates (per 100,000) of all-cause OM outpatient visits in children aged 2–23 months. We used case-based data from the Outpatient Visits Information System of the Unified Health System coded for ICD-10 diagnosis for the period of August/2008 to July/2015. As a comparator, we used rates of outpatient visits due to all-other causes. The relative reduction of all-cause OM and all-other causes of outpatient visits were calculated as the difference between the predicted and observed cumulative rates of the PCV10 post-vaccination period. We then subtracted the relative reduction of all-other causes of outpatient visits from all-cause OM to obtain the impact of PCV10 on OM. In total, 6,401 OM outpatient visits were recorded in 4,793 children aged 2–23 months. Of these, 922 (19.2%) children had more than one OM episode. A significant reduction in all-cause OM visits was observed (50.7%; 95%CI: 42.2–59.2%; p = 0.013), while the reduction in visits due to all-other causes was 7.7% (95% CI 0.8–14.7%; p

Proteinuria is a marker and mediator of chronic kidney disease (CKD). In clinical practice, the urinary protein‐to‐creatinine ratio (UP/C) is of limited usefulness, because it indicates only the magnitude of proteinuria and not the origin of the loss (glomerular or tubular). The complete assessment of proteinuria includes quantitative and qualitative evaluations, both of which are required in order to optimize the therapy. In addition to measuring the UP/C, we performed SDS‐PAGE and western blotting to determine the expression of albumin, vitamin D‐binding protein (VDBP), retinol‐binding protein (RBP), and Tamm‐Horsfall protein (THP) in urine samples of 49 dogs: healthy (control) dogs (n = 9); and dogs with CKD (n = 40), stratified by stage. In the dogs with stage 3 or 4 CKD, there was a predominance of tubular proteins. Neither VDBP nor RBP was observed in the urine of the control dogs. Among the dogs with stage 1 or 2 CKD, VDBP and RBP were detected in those without proteinuria or with borderline proteinuria. The expression of urinary albumin was significantly higher in the stage 4 group than in any other group (P ≤ 0.01). In the stage 4 group, urinary THP was either undetectable or lower than in the control group (P ≤ 0.01). In conclusion, urinary VDBP and RBP might act as early markers of kidney injury, and a decrease in urinary THP could be an indicator of CKD progression.

Background Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats. Methods By clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 × 106 huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49. Results On post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (β-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) and microRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased β-galactosidase expression and increased the expression of Klotho. Conclusions Our data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0475-8) contains supplementary material, which is available to authorized users.

Background: In Latin America, few studies have been carried out on methicillin-resistant Staphylococcus aureus carriage in the pediatric population. We conducted a survey of nasal S. aureus carriage in neonates and in children attending the pediatric outpatient clinics in a large Brazilian city with high antimicrobial consumption. Methods: Pernasal swabs of neonates were collected upon admission and at discharge in four neonatal intensive care units and of children less than five years of age during outpatient visits. Methicillin-resistant S. aureus isolates were characterized for antibiotic susceptibility, mec gene presence, pulsed-field gel electrophoresis, spa type, SCCmec-type, multilocus sequence type, and presence of Panton-Valentine leukocidin genes. Results: S. aureus was carried by 9.1% and 20.1% of the 701 neonates and of 2034 children attending the outpatient clinics, respectively; methicillin-resistant S. aureus carriage was detected in 0.6% and 0.2%, of the these populations, respectively. Healthcare-associated methicillin-resistant S. aureus strains found in neonates from neonatal intensive care units and outpatients were genetically related to the Brazilian (SCCmec-III, ST239) and to the Pediatric (SCCmec-IV, ST5) clones. Community-associated methicillin-resistant S. aureus was only detected in outpatients. None of the methicillin-resistant S. aureus strains contained the Panton-Valentine leukocidin gene. Methicillin-resistant S. aureus strains related to the Brazilian clone showed multidrug resistance pattern. Conclusions: Despite the high antibiotic pressure in our area, and the cross transmission of the healthcare-associated methicillin-resistant S. aureus clones between neonatal intensive care units and outpatients, the prevalence of methicillin-resistant S. aureus carriage is still low in our setting. Keywords: Staphylococcus aureus carriage, Methicillin-resistant Staphylococcus aureus, Neonates, Children

Pneumonia is most problematic for children in developing countries. In 2010, Brazil introduced a 10-valent pneumococcal conjugate vaccine (PCV10) to its National Immunization Program. To assess the vaccine’s effectiveness for preventing pneumonia, we analyzed rates of hospitalization among children 2–24 months of age who had pneumonia from all causes from January 2005 through August 2011. We used data from the National Hospitalization Information System to conduct an interrupted time-series analysis for 5 cities in Brazil that had good data quality and high PCV10 vaccination coverage. Of the 197,975 hospitalizations analyzed, 30% were for pneumonia. Significant declines in hospitalizations for pneumonia were noted in Belo Horizonte (28.7%), Curitiba (23.3%), and Recife (27.4%) but not in São Paulo and Porto Alegre. However, in the latter 2 cities, vaccination coverage was less than that in the former 3. Overall, 1 year after introduction of PCV10, hospitalizations of children for pneumonia were reduced.

Renal dysfunction is common during episodes of acute decompensated heart failure, and historical data indicate that the mean creatinine level at admission has risen in recent decades. Different mechanisms underlying this change over time have been proposed, such as demographic changes, hemodynamic and neurohumoral derangements and medical interventions. In this setting, various strategies have been proposed for the prevention of renal dysfunction with heterogeneous results. In the present article, we review and discuss the main aspects of renal dysfunction prevention according to the different stages of heart failure.

Background Routine infant immunization with meningococcal C conjugate (MCC) vaccination started in Brazil in November 2010, scheduled at three and five months plus a booster at 12–15 months of age. No catch-up was implemented. We assessed the impact of vaccination on meningococcal C disease (MenC) four years after vaccination start in the National Immunization Program. Methods We performed an ecological quasi-experimental design from 2008 to 2014 using a deterministic linkage between the National Notification and the National Reference Laboratory databases for meningitis. We conducted an interrupted time-series analysis considering Brazil except for Salvador municipality, because an epidemic of serogroup C disease occurred in this city, which prompted a mass vaccination campaign with catch-up for adolescents in 2010. Observed MenC rates in the post-vaccination period were compared to expected rates calculated from the pre-vaccination years. Results for Salvador were presented as descriptive data. An additional time-series analysis was performed for the state of Sao Paulo. Results A total of 18,136 MenC cases were analyzed. The highest incidence rates were observed for infants aged

Background In recent decades middle-income countries have experienced a rapid increase in the number of cars and motorcycles. Increased deaths and hospitalizations due to road traffic injuries (RTI) has been observed in several countries as a result. In this study we assessed the determinants of RTIs in Brazil by mode of transportation and compared differences in RTI rates among macro-regions. Methods We used data from the National Health Survey (NHS) conducted in 2013 by the Brazilian Institute of Geography and Statistics and the Ministry of Health. NHS is a comprehensive household survey which includes a representative sample (N = 60,198) of individuals aged 18 years or older. The prevalence and determinants of RTI were estimated according to different modes of transport (car/van, motorcycle, and other) and regions of the country. Bivariate and multivariable logistic regression models were applied to assess crude and adjusted odds ratios, respectively, and their 95 % CI for RTI determinants. Results The prevalence of RTI for the Southeast, South, Central-West, Northeast and North regions of Brazil was 2.4 %, 2.9 %, 4.4 %, 3.4 % and 4.8 %, respectively, pointing to important differences among regions. High percentages of motorcyclists were observed in the Northeast and North regions. For motorcyclists, factors associated with RTIs were being male (OR = 2.6;95 % CI:2.3;3.0), aged 18–29 (OR = 3.2; 95 % CI:2.7;3.8) and 30–39 years (OR = 2.0;95 % CI:1.7;2.5), black (OR = 1.4;95 % CI:1.1;1.7), having elementary educational (OR = 1.5;95 % CI:1.1;1.9), reporting binge drinking behavior (OR = 1.3;95 % CI:1.1;1.5), and living in the Central-West (OR = 2.0;95 % CI:1.6;2.5), Northeast (OR = 1.8;95 % CI:1.5;2.1) and North (OR = 2.0;95 % CI:1.6; 2.5) regions of the country. The independent variables associated with RTI for car/van occupants were being male (OR = 1.7;95 % CI:1.4;2.1), aged 18–29 (OR = 1.5;95 % CI:1.1;2.0) and 30–39 years (OR = 2.5;95 % CI:1.9;3.2), reporting binge drinking behavior (OR = 2.0;95 % CI:1.6;2.5) and living in the South region (OR = 1.6;95 % CI:1.3;2.1). Conclusions There were considerable regional disparities in RTI rates across Brazil’s regions. Motorcyclists contributed to the high RTI rates in these regions as did demographic factors and behaviors such as alcohol use. These findings can help guide interventions to reduce the burden of RTIs in Brazil.

Background In hemorrhagic shock (HS), volume replacement with crystalloid solution can restore the hemodynamic status and decrease mortality. However, it can also lead to tissue edema and pulmonary congestion, as well as increasing vascular permeability. Here, we analyzed the effects that resuscitation with lactated Ringer9s solution (LRS) or administration of the vasopressin analog terlipressin has on renal function in a porcine model of HS. Methods Using pressure-controlled bleeding, we induced pigs to HS, maintaining mean arterial pressure (MAP) at 40 mm Hg for 30 min. Animals were divided into 4 groups: sham (anesthesia only); shock-only (HS induction); shock+LRS (HS induction and subsequent resuscitation with LRS at 3 times the volume of blood removed); and shock+Terli (HS induction and subsequent bolus administration of 2 mg of terlipressin). Parameters were evaluated at baseline, then at 30, 60, and 120 min after treatment (T30, T60, and T120, respectively). Animals were euthanized at T60 or T120. Results Both treatments restored MAP to baseline values. At T30 and T60, creatinine clearance was highest in shock+LRS pigs, whereas it was highest in shock+Terli pigs at T120. Both treatments initially induced hyponatremia, although urinary excretion of all ions was higher in shock+LRS pigs at T30. Both treatments restored Na–K–2Cl cotransporter expression, whereas only terlipressin restored aquaporin 2 expression. Both treatments also prevented HS-induced acute tubular necrosis. Expression of the vasopressin receptors V1a and V2 was highest in shock-only pigs. At T120, V1a expression was lowest in shock+LRS pigs. Discussion Terlipressin might be useful for preventing HS-induced acute kidney injury.

Background Vaccination coverage is the usual metrics to evaluate the immunization programs performance. For the 10-valent pneumococcal conjugate (PCV10) vaccine, measuring the delay of vaccination is also important, particularly as younger children are at increased risk of disease. Routinely collected administrative data was used to assess the timeliness of PCV10 vaccination, and the factors associated with delay to receive the first and second doses, and the completion of the PCV10 3 + 1 schedule. Methods A population-based retrospective cohort study was conducted with children born in 2012 in Central Brazil. Children who received the PCV10 first dose in public health services were followed-up until 23 months of age. Timeliness of receiving each PCV10 dose at any given age was defined as receiving the dose within 28 days grace period from the recommended age by the National Immunization Program. Log-binomial regression models were used to examine risk factors for delays of the first dose and the completion PCV10 3 + 1 schedule. Results In total, 14,282 children were included in the cohort of study. Delayed vaccination occurred in 9.4%, 23.8%, 36.8% and 39.9% children for the first, second, third and the booster doses, respectively. A total of 1912 children (12.8% of the cohort) were not adequately vaccinated at the 6 months of life; 1,071 (7%) received the second dose after 6 months of age, 784 (5.4%) did not receive the second dose, and 57 (0.4%) received the first dose after six months of life. Conclusion A considerable delay was found in PCV10 third and booster doses. Almost 2 thousand children had not received the recommended PCV10 doses at 6 months of age. Timeliness of vaccination is an issue in Brazil although high vaccination coverages.

Introduction Road traffic crashes (RTC) are an important public health problem, accounting for 1.2 million deaths per year worldwide. In Brazil, approximately 40,000 deaths caused by RTC occur every year, with different trends in the Federal Units. However, these figures may be even greater if health databases are linked to police records. In addition, the linkage procedure would make it possible to qualify information from the health and police databases, improving the quality of the data regarding underlying cause of death, cause of injury in hospital records, and injury severity. Objective This study linked different data sources to measure the numbers of deaths and serious injuries and to estimate the percentage of corrections regarding the underlying cause of death, cause of injury, and the severity injury in victims in matched pairs from record linkage in five representative state capitals of the five macro-regions of Brazil. Methods This cross-sectional, population-based study used data from the Hospital Information System (HIS), Mortality Information System (MIS), and Police Road Traffic database of Belo Horizonte, Campo Grande, Curitiba, Palmas, and Teresina, for the year 2013 for Teresina, and 2012 for the other capitals. RecLink III was used to perform probabilistic record linkage by identifying matched pairs to calculate the global correction percentage of the underlying cause of death, the circumstance that caused the road traffic injury, and the injury severity of the victims in the police database. Results There was a change in the cause of injury in the HIS, with an overall percentage of correction estimated at 24.4% for Belo Horizonte, 96.9% for Campo Grande, 100.0% for Palmas, and 33.2% for Teresina. The overall percentages of correction of the underlying cause of death in the MIS were 29.9%, 11.9%, 4.2%, and 33.5% for Belo Horizonte, Campo Grande, Curitiba, and Teresina, respectively. The correction of the classification of injury severity in police database were 100.0% for Belo Horizonte and Teresina, 48.0% for Campo Grande, and 51.4% for Palmas after linkage with hospital database. The linkage between mortality and police database found a percentage of correction of 29.5%, 52.3%, 4.4%, 74.3 and 72.9% for Belo Horizonte, Campo Grande, Palmas, Curitiba and Teresina, respectively in the police records. Conclusions The results showed the importance of linking records of the health and police databases for estimating the quality of data on road traffic injuries and the victims in the five capital cities studied. The true causes of death and degrees of severity of the injuries caused by RTC are underestimated in the absence of integration of health and police databases. Thus, it is necessary to define national rules and standards of integration between health and traffic databases in national and state levels in Brazil.

Although sepsis outcomes are relatively well known for developed countries, very few studies evaluated the long-term prognosis of septic patients at a national level in developing countries.

BACKGROUND: Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health.METHODS: We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non-severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate.RESULTS: We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low- and-middle income countries (LMIC) and high-income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5-8.7), US$ 51.7 (95% CI 17.4-91.0) and US$ 242.7 (95% CI 153.6-341.4)-559.4 (95% CI 268.9-886.3) in community, out-patient facilities and different levels of hospital in-patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%-115.8% of patients' monthly household income in LMIC. The mean direct non-medical cost and indirect cost for severe pneumonia management accounted for 0.5-31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3-6.4) and 7.7 (IQR 5.5-9.9) days in LMIC and HIC respectively for these children.CONCLUSION: This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.

Routine infant immunization with 10-valent pneumococcal conjugate vaccine (PCV-10) began in Brazil in 2010. The impact of the PCV-10 on rates of invasive pneumococcal disease (IPD) at the population level was not yet evaluated. Serotype-specific IPD changes after PCV-10 introduction is still to be determined. Data from national surveillance system for notifiable diseases (SINAN) and national reference laboratory for S. pneumoniae in Brazil (IAL) were linked to enhance case ascertainment of IPD. An interrupted time-series analysis was conducted to predict trends in the postvaccination IPD rates in the absence of PCV-10 vaccination, taking into consideration seasonality and secular trends. PCVs serotype-specific distribution were assessed before (2008-2009) and after (2011-2013) the introduction of PCV-10 in the immunization program. A total of 9,827 IPD cases were identified from 2008-2013 when combining SINAN and IAL databases. Overall, PCV-10 types decreased by 41.3% after PCV-10 vaccination period, mostly in children aged 2-23 months, while additional PCV-13 serotypes increased by 62.8% mainly in children under 5-year of age. For children aged 2-23 months, targeted by the immunization program, we observed a 44.2% (95%CI, 15.8-72.5%) reduction in IPD rates. In contrast, significant increase in IPD rates were observed for adults aged 18-39 y (18.9%, 95%CI 1.1-36.7%), 40-64 y (52.5%, 95%CI 24.8-80.3%), and elderly ≥ 65 y (79.3%, 95%CI 62.1-96.5%). This is the first report of a time-series analysis for PCV impact in IPD conducted at national level data in a developing country. We were able to show significant impact of PCV-10 on IPD for age groups targeted by vaccination in Brazil, 3 y after its introduction. No impact on other age groups was demonstrated.

Background Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. Methods In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups—SLED (n = 19) and SLEDf (n = 20)—evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. Results During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%). Conclusions The mode of dialysis clearance might not affect outcomes in severe leptospirosis.

Background and objectives: There have been few studies investigating acute kidney injury (AKI) in patients infected with the 2009 pandemic influenza A (H1N1) virus. Therefore, the objective of this study was to identify the factors associated with AKI in H1N1-infected patients. Design, setting, participants, & measurements: This was a study of 47 consecutive critically ill adult patients with reverse transcriptase-PCR-confirmed H1N1 infection in Brazil. Outcome measures were AKI (as defined by the Risk, Injury, Failure, Loss, and End-stage renal failure [RIFLE] criteria) and in-hospital death. Results: AKI was identified in 25 (53%) of the 47 H1N1-infected patients. AKI was associated with vasopressor use, mechanical ventilation, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and severe acidosis as well as with higher levels of C-reactive protein and lactic dehydrogenase upon intensive care unit (ICU) admission. A nephrology consultation was requested for 16 patients (64%), and 8 (50%) required dialysis. At ICU admission, 7 (15%) of the 25 AKI patients had not yet progressed to AKI. However, by 72 hours after ICU admission, no difference in RIFLE score was found between AKI survivors and nonsurvivors. Of the 47 patients, 9 (19%) died, all with AKI. Mortality was associated with mechanical ventilation, vasopressor use, dialysis, high APACHE II score, high bilirubin levels, and a low RIFLE score at ICU admission. Conclusions: Among critically ill H1N1-infected patients, the incidence of AKI is high. In such patients, AKI is mainly attributable to shock.

Progressive renal failure continues to be a challenge. The use of bone marrow cells represents a means of meeting that challenge. We used lineage-negative (Lin−) cells to test the hypothesis that Lin− cell treatment decreases renal injury. Syngeneic Fischer 344 rats were divided into four groups: sham (laparotomy only, untreated); Nx (five-sixth nephrectomy and untreated); NxLC1 (five-sixth nephrectomy and receiving 2 × 106 Lin− cells on postnephrectomy day 15); and NxLC3 (five-sixth nephrectomy and receiving 2 × 106 Lin− cells on postnephrectomy days 15, 30, and 45). On postoperative day 16, renal mRNA expression of interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 was lower in NxLC rats than in Nx rats. On postnephrectomy day 60, NxLC rats presented less proteinuria, glomerulosclerosis, anemia, renal infiltration of immune cells, and protein expression of monocyte chemoattractant protein-1, as well as decreased interstitial area. Immunostaining for proliferating cell nuclear antigen showed that, in comparison with sham rats, Nx rats presented greater cell proliferation, whereas NxLC1 rats and NxLC3 rats presented less cell proliferation than did Nx rats. Protein expression of the cyclin-dependent kinase inhibitor p21 and of vascular endothelial growth factor increased after nephrectomy and decreased after Lin− cell treatment. On postnephrectomy day 120, renal function (inulin clearance) was significantly better in Lin− cell-treated rats than in untreated rats. Lin− cell treatment significantly improved survival. These data suggest that Lin− cell treatment protects against chronic renal failure.

Tenofovir disoproxil fumarate (TDF) is a first-line drug used in patients with highly active retroviral disease; however, it can cause renal failure associated with many tubular anomalies that may be due to down regulation of a variety of ion transporters. Because rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist induces the expression of many of these same transporters, we tested if the nephrotoxicity can be ameliorated by its use. High doses of TDF caused severe renal failure in rats accompanied by a reduction in endothelial nitric-oxide synthase and intense renal vasoconstriction; all of which were significantly improved by rosiglitazone treatment. Low-dose TDF did not alter glomerular filtration rate but produced significant phosphaturia, proximal tubular acidosis, polyuria and a reduced urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. A Fanconi's-like syndrome was ruled out as there was no proteinuria or glycosuria. Rosiglitazone reversed TDF-induced tubular nephrotoxicity, normalized urinary biochemical parameters and membrane transporter protein expression. These studies suggest that rosiglitazone treatment might be useful in patients presenting with TFV-induced nephrotoxicity especially in those with hypophosphatemia or reduced glomerular filtration rate.

Pneumocystis carinii pneumonia is a serious and relatively common complication of immunosuppressive therapy. In immunocompromised patients, P. carinii pneumonia can cause significant morbidity and mortality. Another common complication, typically seen in the subpopulation of renal transplant recipients, is hypercalcemia. The prevalence of hypercalcemia varies, reaching as high as 71%. We report the case of a renal transplant recipient who developed P. carinii pneumonia and hypercalcemia, the latter being resolved after the successful treatment of the former. We argue that there is a causal relationship between P. carinii pneumonia and hypercalcemia in renal transplant recipients. In immunocompromised patients, pulmonary infection accompanied by hypercalcemia should raise the suspicion of P. carinii pneumonia.

Background Severe scorpion envenomation can evolve to lung injury and, in some cases, death. The lung injury could be attributed to acute left ventricular failure and increased pulmonary vascular permeability secondary to the release of inflammatory mediators. In clinical practice, corticosteroids have been administered to reduce the early side effects of the anti-venom. We propose to study the effects of Tityus serrulatus venom and dexamethasone on pulmonary expression of sodium and water transporters, as well as on the inflammatory response. Methods Wistar rats were injected intraperitoneally with saline (control group), dexamethasone, and saline (2.0 mg/kg body weight—60 min before saline injection; dexamethasone + saline group), venom (T. serrulatus venom—3.8 mg/kg body weight), or dexamethasone and venom (2.0 mg/kg body weight—60 min before venom injection; dexamethasone + venom group). At 60 min after venom/saline injection, experiments were performed in ventilated and non-ventilated animals. We analyzed sodium transporters, water transporters, and Toll-like receptor 4 (TLR4) by Western blotting, macrophage infiltration by immunohistochemistry, and serum interleukin (IL) by cytokine assay. Results In the lung tissue of non-ventilated envenomed animals, protein expression of the epithelial sodium channel alpha subunit (α-ENaC) and aquaporin 5 (AQP5) were markedly downregulated whereas that of the Na-K-2Cl cotransporter (NKCC1) and TLR4 was elevated although expression of the Na,K-ATPase alpha 1 subunit was unaffected. Dexamethasone protected protein expression of α-ENaC, NKCC1, and TLR4 but not that of AQP5. We found that IL-6, IL-10, and tumor necrosis factor alpha were elevated in the venom and dexamethasone + venom groups although CD68 expression in lung tissue was elevated only in the venom group. Among the ventilated animals, both envenomed groups presented hypotension at 50 min after injection, and the arterial oxygen tension/fraction of inspired oxygen ratio was lower at 60 min than at baseline. Conclusions Our results suggest that T. serrulatus venom and dexamethasone both regulate sodium transport in the lung and that T serrulatus venom regulates sodium transport via the TLR4 pathway.

In Brazil, 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in 2010 in the childhood routine immunization program. We used primary data to evaluate the effect of PCV10 on the reduction of hospital admissions due to community-acquired pneumonia (CAP).Active population-based surveillance studies on pneumonia hospitalizations in children aged36 months were conducted before and after PCV10 introduction in Central Brazil. The surveillances comprised all 17 pediatric hospitals of the study area, which provide assistance for public and private health insurances. Linear regression was performed to detect any trend in pneumonia monthly rates previously to vaccine introduction. PCV10 post-vaccination impact (Nov/2011 to Oct/2013) on clinical and X-Ray confirmed pneumonia was estimated as the relative and the absolute reduction (prevented burden) in pneumonia admission rates, taking as baseline the pre-vaccination period (May/2007 to Apr/2009).Overall, males presented higher rates of pneumonia hospitalization, compared to females. The relative rate reduction for clinical and X-Ray confirmed pneumonia was 13.1%, and 25.4%, respectively for children aged 2-23 months. The highest prevented burden was observed in age-groups 2-11 months, respectively 853/100,000 (from 6788/100,000 to 5935/100,000), and 729/100,000 (from 2871/100,000 to 2142/100,000), for clinical and X-Ray confirmed pneumonia.This study provides evidence for the impact of PCV10 in clinical and X-Ray confirmed pneumonia in routine vaccination program in Brazil, after 3 years of vaccine introduction. Extended follow-up studies should confirm the benefit of vaccination through herd effect given the high burden of pneumonia in our setting.

Pneumococcal 10-valent conjugate vaccine (PCV10) was introduced to Brazil’s National Immunization Program (NIP) in 2010. During the first year of vaccine introduction three schedules were used to deal with age at initiation of PCV for catch-up purposes: 3 primary doses + 1 booster (for children aged ≤6 months), a catch-up schedule of 2 doses + 1 booster (7-11 months), and a catch-up schedule of a single dose (12-15 months). The purpose of this study was to assess the magnitude and associated risk factors for under-vaccination or lack of on time vaccination six to eight months after PCV10 introduction. A household survey was conducted in the municipality of Goiania with 1,237 children, who were retroactively classified into one of three age groups, as a factor of the child’s age relatively to 30 days after PCV10 introduction. Socioeconomic characteristics and vaccination dates were obtained during home interviews. Vaccination coverage was defined as the percentage of children who completed the recommended number of doses. Compliance with recommended schedules was defined as the percentage of children who received all valid doses at the NIP recommended time interval. Adjusted prevalence ratios (PR) of variables independently associated with coverage and compliance were estimated by log binomial regression. Coverage of DTP-Hib was used for comparison purposes. Overall, vaccination coverage was 54.6% (95% CI 52.1-57.7%), lower than DTP-Hib coverage (93.0%; 95% CI 91.5-94.3%). Compliance with recommended schedules was 16.8% (95% CI: 14.7-18.6%). Children 7-11 months old had lower coverage (40.7%) and compliance (6.3%) compared to children aged 12-15 months (coverage: 88.8%; compliance: 35.6%) and ≤6 months old (coverage: 54%; compliance: 18.8%). Having private health insurance was associated with higher PCV10 coverage (PR=1.25; 95% CI: 1.06-1.47, p=0.007), and compliance (PR=1.09; 95% CI: 1.02-1.16, p=0.015). Although PCV10 coverage rapidly increased shortly after vaccination introduction, it was not matched by compliance with recommended schedules. Public initiatives should target compliance of PCV10 because of the burden of pneumococcal diseases on childhood morbidity and mortality.

Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI.

OBJECTIVE To identify evidence of the impact of Haemophilus influenzae type b (Hib) conjugate vaccine on the epidemiology of invasive Hib disease. SOURCES OF DATA This review was based on a search of MEDLINE, LILACS, technical reports, national and international guidelines (publications from 1991 to 2005). The keywords Haemophilus influenzae type b, immunization, impact, and effectiveness, alone or in combination, were used to retrieve the articles. Studies published before 1991 and cited in the references of the studies reviewed were analyzed for useful information. SUMMARY OF THE FINDINGS Introduction of the Hib conjugate vaccine produced great decline in the incidence of invasive Hib disease in childhood in countries where this vaccine was introduced into the routine immunization schedule. Nevertheless, the resurgence of invasive Hib disease in some regions has challenged several researchers to identify the reasons for this epidemiological pattern, as well as the measures to be implemented in order to avoid such a phenomenon. CONCLUSIONS The use of Hib conjugate vaccine on a population scale has been greatly effective; nonetheless, changes in the vaccination scheme seem to be necessary to keep invasive Hib disease under control.

Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia+magnesium, ischemia+NAC, and ischemia+magnesium+NAC. GFR (inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone.

OBJETIVO: Identificar fatores prognosticos de mortalidade neonatal em unidades de cuidados intensivos. METODOS: Realizou-se estudo de coorte de nascidos vivos do municipio de Goiânia, no periodo de novembro de 1999 a outubro de 2000. Procedeu-se a vinculacao das bases de dados das declaracoes de nascidos vivos e de obitos, das quais as variaveis de exposicao foram extraidas. Adicionalmente, foi implementado um sistema ativo de vigilância de mortalidade neonatal. A variavel de efeito foi constituida dos recem-nascidos admitidos nas unidades de cuidados intensivos que sobreviveram (n=713) e dos que morreram (n=162). Utilizou-se o modelo de regressao de Cox para identificar fatores associados a mortalidade neonatal e a curva Receiver Operating Characteristic para avaliar a acuracia de variaveis estatisticamente significantes em modelo multivariado. Taxas de mortalidade ajustadas por peso de nascimento e Apgar do quinto minuto foram calculadas para cada unidade de cuidados intensivos. RESULTADOS: Baixo peso ao nascer e Apgar do quinto minuto permaneceram associados ao obito neonatal, de forma independente. Peso ao nascer igual a 2.500 g apresentou acuracia de 0,71 (IC 95%: 0,65-0,77) na predicao de obito neonatal (sensibilidade =72,2%). Observou-se ampla variacao nas taxas de mortalidade entre as unidades de cuidados intensivos (9,5%-48,1%) sendo que duas delas permaneceram com taxas significantemente mais altas apos o ajuste da mortalidade pelo peso de nascimento e Apgar. CONCLUSOES: Os resultados mostraram que o peso de nascimento e uma variavel sensivel para uso em triagens em programas de vigilância de obito neonatal e pode identificar as unidades de cuidados intensivos com altas taxas de mortalidade para implementacao de acoes preventivas e para intervencoes no periodo intra-parto.

Urban dengue fever is now considered a major public health threat in most American countries. A household survey was conducted in the city of Goiânia in central Brazil in 2001 to assess prevalence of dengue infection and individual and area-based risk factors. Spatial point pattern analysis was performed using the dual Kernel method. A total of 1,610 households were surveyed; 1,585 individuals more than five years old had blood and data collected. Sera were tested for IgM/IgG antibodies by an enzyme-linked immunoassay. Area-based indicators derived from census data were linked to geocoded residential address. The seroprevalence of dengue was 29.5% and the estimate prevalence surface reached 50% in the outskirts areas. The risk of infection was significantly associated with older age (P < 0.01), low education (odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.82–6.55), and low income (OR = 1.32, 95% CI = 1.02–1.71) in multivariate analysis. This study highlighted the heterogeneity of dengue transmission within the city and can assist in spatial targeting control interventions.

Background. N-Acetylcysteine has been shown to protect against contrast nephropathy, although the mechanisms underlying such an effect are unclear. Surprisingly, studies have shown that post-radiocontrast renal function actually improves in chronic renal failure patients receiving N-acetylcysteine. However, there have been no studies investigating the cause of this improvement. Methods. In a double-blind, placebo-controlled study, 24 patients (aged 65±2 years) suffering from stable mild-to-moderate renal insufficiency and undergoing elective coronary angiography were randomized to receive either placebo or N-acetylcysteine. All received similar hydration. Renal function parameters were assessed 48 h before and 48 h after radiocontrast administration. Urinary 15-isoprostane F2t, a specific marker of oxidative stress, was measured immediately before and after the procedure. Expression of urinary a-glutathione S-transferase protein, a specific proximal tubular injury marker, was assessed after the procedure. Results. Comparing creatinine clearance values before and after angiography, a significant increase was seen in N-acetylcysteine patients (44.7±4.2 vs 57.2±6.3 ml/min/1.73 m 2 ; P ¼ 0.02), whereas placebo patients presented no change (46.6±5.0 vs 46.9± 4.3 ml/min/1.73 m 2 ; P ¼ 0.90). After radiocontrast, urinary 15-isoprostane F2t levels in placebo patients increased significantly over baseline values (2.9±0.7 vs 10.3±2.1 ng/mg creatinine; P ¼ 0.007), whereas urinary 15-isoprostane F2t levels in N-acetylcysteine patients remained basically unchanged (3.5±0.5 vs 4.1±0.9 ng/mg creatinine; P ¼ 0.63). Furthermore, N-acetylcysteine treatment led to lower levels of a-glutathione S-transferase than did placebo treatment (0.8±0.2 vs 2.4±0.7mg/g; P ¼ 0.046). Conclusions. In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury.

BACKGROUND The conjugate Haemophilus influenzae type b (Hib) vaccine has been highly efficacious in reducing type b H. influenzae meningitis. However, information is limited about its impact on childhood pneumonia after vaccine introduction into the routine programme. This study evaluated the effectiveness of Hib conjugate vaccine in the reduction of community-acquired pneumonia among infants in Central Brazil. METHODS A matched case-control study was built into an ongoing prospective population-based surveillance of pneumonia, enrolling 1293 participants between May 2000 and August 2001. Cases (n = 431) were children