Early warnings of heart rate deterioration

Hospitals can experience difficulty in detecting and responding to early signs of patient deterioration leading to late intensive care referrals, excess mortality and morbidity, and increased hospital costs. Our study aims to explore potential indicators of physiological deterioration by the analysis of vital-signs. The dataset used comprises heart rate (HR) measurements from MIMIC II waveform database, taken from six patients admitted to the Intensive Care Unit (ICU) and diagnosed with severe sepsis. Different indicators were considered: 1) generic early warning indicators used in ecosystems analysis (autocorrelation at-1-lag (ACF1), standard deviation (SD), skewness, kurtosis and heteroskedasticity) and 2) entropy analysis (kernel entropy and multi scale entropy). Our preliminary findings suggest that when a critical transition is approaching, the equilibrium state changes what is visible in the ACF1 and SD values, but also by the analysis of the entropy. Entropy allows to characterize the complexity of the time series during the hospital stay and can be used as an indicator of regime shifts in a patient’s condition. One of the main problems is its dependency of the scale used. Our results demonstrate that different entropy scales should be used depending of the level of entropy verified.

Regional Variation on Rates of Bronchopulmonary Dysplasia and Associated Risk Factors

Background. An abnormally high incidence (44%) of bronchopulmonary dysplasia with variations in rates among cities was observed in Colombia among premature infants. Objective. To identify risk factors that could explain the observed high incidence and regional variations of bronchopulmonary dysplasia. Study Design. A case-control study was designed for testing the hypothesis that differences in the disease rates were not explained by differences in city-of-birth specific population characteristics or by differences in respiratory management practices in the first 7 days of life, among cities. Results. Multivariate analysis showed that premature rupture of membranes, exposure to mechanical ventilation after received nasal CPAP, no surfactant exposure, use of rescue surfactant (instead of early surfactant), PDA, sepsis and the median daily FIO2, were associated with a higher risk of dysplasia. Significant differences between cases and controls were found among cities. Models exploring for associations between city of birth and dysplasia showed that being born in the highest altitude city (Bogotá) was associated with a higher risk of dysplasia (OR 1.82 95% CI 1.31–2.53). Conclusions. Bronchopulmonary dysplasia was manly explained by traditional risk factors. Findings suggest that altitude may play an important role in the development of this disease. Prenatal steroids did not appear to be protective at high altitude.

Sinalização endógena do sistema Nociceptina/Orfanina FQ - receptor NOP: envolvimento na modulação da depressão experimental induzida por lipopolissacarídeo

During the last decades, it has been established that there is a relationship between major depression and activation of immune system. Nociceptin/orphanin FQ (N/OFQ) is the natural ligand of a Gi-protein coupled receptor named NOP, both compose the peptidergic system wich is involved in the regulation of mood states and inflammatory responses. Considering these actions, the present thesis aimed to investigate the consequences of blocking NOP signaling in lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors in mice. Systemic administration of LPS doses, that do not cause sepsis in mice, induce changes in their behaviors related with activity of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukins 6 (IL-6) and 1β (IL-1 β). At the time points of 2 to 6 h and 24 h after intraperitoneal injection, mice treated with LPS displayed, respectively, sickness and depressive-like behaviors. In the present work the administration of LPS 0.8 mg/kg (ip) significantly induced sickness signs in Swiss and CD-1 mice, such as weight loss, transient reduction in rectal temperature and decrease of food and water intake. Moreover at 24 h after LPS injection these same mice strains displayed significantly increased immobility time on the tail suspension test (TST) when compared with control mice, this alteration was not related with possible locomotion impairments as verified on the open field test. Treatment with Nortriptyline 30 mg/kg (ip, 60 min prior the TST) reduced the immobility time of control and LPS-treated mice and was used as standard antidepressant. The NOP receptor antagonist SB-612111 (10 mg/kg, ip), 30 min prior LPS, did not modify LPS-induced sickness signs and depressive-like behavior. However, when injected 24 h after LPS treatment, SB-612111 (ip, 30 min prior the TST) as well as the peptidergic NOP receptor antagonist UFP-101 (10 nmol/2μL, icv, 5 min prior the TST) significantly reversed the toxin effects. The protocol of LPS-induced depressive-like states was also tested in NOP receptor knockout mice (NOP(-/-)) and their respective wild types (NOP(+/+)). LPS evoked transient rectal temperature reduction in NOP(-/-) mice and loss of body weight, food and water intake reduction in both NOP(+/+) and NOP(-/-) mice. The consumption of water was significantly different due to the genotype. LPS injection induced transient changes in pro-inflammatory cytokines. At 6 h after LPS injection, serum levels of TNF-α were significantly increased in NOP(+/+) and NOP(-/-) mice, as the IL-6 levels were significantly increased just in NOP(+/+) serum. At 24 h after LPS treatment the pro-inflammatory cytokines had returned to the baseline levels in both genotypes. LPS treatment elicited depressive-like effects in NOP(+/+) but not in NOP(-/-) mice. The data obtained during the execution of this doctoral thesis reveal that pharmacological and genetic blockade of NOP signaling does not affect LPS evoked sickness signs while reversing depressive-like behavior. In conclusion, these results highlight the involvement of the peptidergic system N/OFQ - NOP receptor in the modulation of behaviors related to mood and activation of the immune system.

Gasto com a internação de idosos em unidades de terapia intensiva

Introduction: Population aging in Brazil underscores the need to discuss the proper management of the budget allocated in health field, especially in the sectors of high complexity, where coexist costly procedures, limited resources and the need for cost containment. In the other hand, demand is growing in a way directly proportional to the increase in the number of elderly in country. Objective: In this way, this research had as main objective to analyze the costs resulting from the admission of elderly in intensive care units (ICU) and its associated factors. Methods: This is a cross-sectional study with a quantitative approach and featured as a descriptive and exploratory research. Data were collected from medical records of elderly hospitalized in ICU from a brazilian city called Natal-RN, between november first, 2013 and january, 31 of 2014. The variables collected relate to the socio demographic profile, morbidity framework and characterization of hospitalization. The dependent variable was categorized by quartile 75 in high and low expense of hospitalization and submitted to chi-square test with the independent variables of the survey. Associations with p value <0.20 in the bivariate analysis were submitted to the technique of multiple logistic regression. We opted for the construction of three regression models from the above algorithm: general regression model, composed by all 493 hospitalizations in the study, other made with 181 individuals admitted in health public system (SUS) and a third one related to 312 cases from private service in health area. Results: In the general regression model, the variables respiratory diseases, hospitalizations in the private system, disoriented patient and previous stroke were associated with greater probability of high spending in the ICU. In the other hand, in SUS kind of hospitalizations, this probability was associated with disoriented patient, 80 years old or more, sepsis and admission for clinical reason. In the cases from the private network health, the high expenditure was associated with respiratory disease, mechanical ventilation, hospitalization for clinical reason and disoriented patients. Conclusion: The increased expenditure on hospitalization of elderly in intensive care depends on the clinical conditions of individuals. This highlights the importance of avoiding hospitalizations due to diseases sensitive to primary care by health preventive actions and providing comprehensive care to the elderly. In addition, obtaining different explanatory models, according to kind hospital funding, demonstrates the importance of the organization in health services related to composition of costs of hospitalization among the elderly. Another question founded was the need that to improve the funding, we must use rationally the available resources by avoiding unnecessary hospitalizations of elderly people in the extremes of severity. On this kind of precarious funding, ICU hospitalization of elderly non-critical or in a terminal state can compromise the quality of services provided to those who really need intensive care.

Protocolo para assistência do enfermeiro ao paciente séptico em terapia intensiva: construção e validação de conteúdo

Tratar-se-á de um estudo metodológico, com abordagem quantitativa; baseado no referencial metodológico da técnica Delphi, com objetivo de construir e validar um protocolo clínico para assistência do enfermeiro ao paciente séptico na Unidade de Terapia Intensiva. A proposta metodológica seguiu duas etapas: elaboração do instrumento por meio da revisão integrativa da literatura e validação de conteúdo do protocolo. O estudo foi aprovado pelo Comitê de Ética em Pesquisa, mediante o Parecer CAAE 41873314.5.0000.5537. O universo amostral foi composto por profissionais enfermeiros, considerados peritos, doutores ou mestres na área da saúde, com experiência em alta complexidade e/ ou estudos de validação de instrumento/protocolo, selecionados por meio da Plataforma Lattes. Referente à primeira etapa elaborou-se um instrumento composto pela caracterização profissional dos peritos; e baseado em evidência científica e nas diretrizes do Surviving Sepsis Campaign, contemplando três tópicos assistenciais ao paciente com sepse, a saber: Triagem para Sepse- Reconhecimento das Manifestações Clínicas; Pacote de Ressuscitação Inicial (Controle das Primeiras 6 Horas); Tratamento de Suporte. A segunda etapa caracterizou-se na validação de conteúdo do instrumento para elaboração final do protocolo, utilizando à técnica Delphi, em duas fases. No que concernem as variáveis referentes ao estudo, na 1ª fase de Delphi, 34 peritos avaliaram o instrumento composto por 18 itens, no período de maio a julho de 2015, e os dados foram analisados pela estatística descritiva (frequência, média, mediana e desvio padrão) e pelo Índice de Validade de Conteúdo (IVC), demonstrando um IVC extremamente satisfatório para 15 itens, com total de 0,79, obtendo assim, a reformulação e refinamento do conteúdo do instrumento. Na segunda fase de Delphi, entre julho e agosto de 2015, participaram 26 peritos, e utilizou-se o percentual de concordância acima de 75% para as variáveis consideradas pertinentes ao protocolo de cuidados ao paciente séptico em UTI, obtendo nesta fase, o percentual de concordância de 95%. O protocolo foi concluído com 15 itens, sendo respaldado e modificado, baseado em evidência científica, nas diretrizes internacionais e nas sugestões dos peritos. A utilização do protocolo proposto poderá contribuir para a prática clínica do enfermeiro ao paciente séptico na Unidade de Terapia Intensiva.

Protocolo para assistência do enfermeiro ao paciente séptico em terapia intensiva: construção e validação de conteúdo

Tratar-se-á de um estudo metodológico, com abordagem quantitativa; baseado no referencial metodológico da técnica Delphi, com objetivo de construir e validar um protocolo clínico para assistência do enfermeiro ao paciente séptico na Unidade de Terapia Intensiva. A proposta metodológica seguiu duas etapas: elaboração do instrumento por meio da revisão integrativa da literatura e validação de conteúdo do protocolo. O estudo foi aprovado pelo Comitê de Ética em Pesquisa, mediante o Parecer CAAE 41873314.5.0000.5537. O universo amostral foi composto por profissionais enfermeiros, considerados peritos, doutores ou mestres na área da saúde, com experiência em alta complexidade e/ ou estudos de validação de instrumento/protocolo, selecionados por meio da Plataforma Lattes. Referente à primeira etapa elaborou-se um instrumento composto pela caracterização profissional dos peritos; e baseado em evidência científica e nas diretrizes do Surviving Sepsis Campaign, contemplando três tópicos assistenciais ao paciente com sepse, a saber: Triagem para Sepse- Reconhecimento das Manifestações Clínicas; Pacote de Ressuscitação Inicial (Controle das Primeiras 6 Horas); Tratamento de Suporte. A segunda etapa caracterizou-se na validação de conteúdo do instrumento para elaboração final do protocolo, utilizando à técnica Delphi, em duas fases. No que concernem as variáveis referentes ao estudo, na 1ª fase de Delphi, 34 peritos avaliaram o instrumento composto por 18 itens, no período de maio a julho de 2015, e os dados foram analisados pela estatística descritiva (frequência, média, mediana e desvio padrão) e pelo Índice de Validade de Conteúdo (IVC), demonstrando um IVC extremamente satisfatório para 15 itens, com total de 0,79, obtendo assim, a reformulação e refinamento do conteúdo do instrumento. Na segunda fase de Delphi, entre julho e agosto de 2015, participaram 26 peritos, e utilizou-se o percentual de concordância acima de 75% para as variáveis consideradas pertinentes ao protocolo de cuidados ao paciente séptico em UTI, obtendo nesta fase, o percentual de concordância de 95%. O protocolo foi concluído com 15 itens, sendo respaldado e modificado, baseado em evidência científica, nas diretrizes internacionais e nas sugestões dos peritos. A utilização do protocolo proposto poderá contribuir para a prática clínica do enfermeiro ao paciente séptico na Unidade de Terapia Intensiva.

Impacto na epidemiologia da sepse tardia após a mudança do protocolo de antimicrobianos em uma UTIN de um serviço universitário

Advances in neonatology resulted in reducing the mortality rate and the consequent increase in survival of newborn pre terms (PTN). On the other hand, there was also a considerable increase in the risk of developing health care-related infection (HAI) in its most invasive, especially for bloodstream. This situation is worrying, and prevent the occurrence of it is a challenge and becomes one of the priorities in the Neonatal Intensive Care Unit (NICU). Sepsis is the main cause of death in critical neonates and affects more than one million newborns each year, representing 40% of all deaths in neonates. The incidence of late sepsis can reach 50% in NICUs. Currently the major responsible for the occurrence of sepsis in developed countries is the coagulase negative Staphylococcus (CoNS), followed by S. aureus. The cases of HAIs caused by resistant isolates for major classes of antimicrobial agents have been increasingly frequent in the NICU. Therefore, vancomycin has to be prescribed more frequently, and, today, the first option in the treatment of bloodstream infections by resistant Staphylococcus. The objectives of this study were to assess the impact on late sepsis in epidemiology III NICU after the change of the use of antimicrobials protocol; check the frequency of multiresistant microorganisms; assess the number of neonates who came to death. This study was conducted in NICU Level III HC-UFU. three study groups were formed based on the use of the proposed late sepsis treatment protocol, with 216 belonging to the period A, 207 B and 209 to the C. The work was divided into three stages: Period A: data collected from neonates admitted to the unit between September 2010 to August 2011. was using treatment of late sepsis: with oxacillin and gentamicin, oxacillin and amikacin, oxacillin and cefotaxime. Period B: data were collected from March 2012 to February 2013. Data collection was started six months after protocol change. Due to the higher prevalence of CoNS, the initial protocol was changed to vancomycin and cefotaxime. Period C: data were collected from newborns inteerne in the unit from September 2013 to August 2014. Data collection was started six months after the protocol change, which occurred in March 2013. From the 632 neonates included in this study, 511 (80,8%) came from the gynecology and obstetrics department of the HC-UFU. The mean gestational age was 33 weeks and the prevailing sex was male (55,7%). Seventy-nine percent of the studied neonates were hospitalized at the NICU HC-UFU III because of complications related to the respiratory system. Suspicion of sepsis took to hospitalization in the unit of 1,9% of newborns. In general, the infection rate was 34,5%, and the most frequent infectious sepsis syndrome 81,2%. There was a tendency to reduce the number of neonates who died between periods A 11 and C (p = 0,053). From the 176 cases of late sepsis, 73 were clinical sepsis and 103 had laboratory confirmation, with greater representation of Gram positive bacteria, which corresponded to 67.2% of the isolates and CoNS the most frequent micro-organism (91,5%). There was a statistically significant difference in the reduction of isolation of Gram positive microorganisms between periods A and C (p = 0,0365) as well as in reducing multidrug-resistant CoNS (A and B period p = 0,0462 and A and C period, p = 0,158). This study concluded that: the CoNS was the main microorganism responsible for the occurrence of late sepsis in neonates in the NICU of HC-UFU; the main risk factors for the occurrence of late sepsis were: birth weight <1500 g, use of PICC and CUV, need for mechanical ventilation and parenteral nutrition, SNAPPE> 24 and length of stay more than seven days; the new empirical treatment protocol late sepsis, based on the use of vancomycin associated cefepime, it was effective, since promoted a reduction in insulation CoNS blood cultures between the pre and post implementation of the Protocol (A and C, respectively); just as there was a reduction in the number of newborns who evolved to death between periods A and C.

"Procalcitonine et protéine C-réactive comme marqueurs des infections bactériennes : une revue systématique et une méta-analyse"

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Caesarean wound care for midwives

With a rise in caesarean births there is a rise in wound care management issues for midwives and the potential for surgical site infections (SSIs). The burden of SSIs include increases in maternal mortality, morbidity, length of hospital stay and cost. Sepsis is currently the leading cause of maternal mortality, with 50 per cent of the women who die having had a caesarean birth (Centre for Maternal and Child Enquiries (CMACE) 2011). Wound management and the prevention of sepsis are therefore issues of great concern to midwives. This article considers the incidence of wound infections and presents the guidance available to help address this problem.

An investigation of the molecular interactions between statins and bacterial pathogens, and their combined impact on the human immune system

Statins are a class of drug that inhibits cholesterol biosynthesis, and are used to treat patients with high serum cholesterol levels. They exert this function by competitively binding to the enzyme 3-hydroxy-3-methylglutaryl-CoenzymeA reductase (HMGR), which catalyses the formation of mevalonate, a rate-limiting step in cholesterol biosynthesis. In addition, statins have what are called “pleiotropic effects”, which include the reduction of inflammation, immunomodulation, and antimicrobial effects. Statins can also improve survival of patients with sepsis and pneumonia. Cystic fibrosis (CF) is the most common recessive inherited disease in the Caucasian population, which is characterised by factors including, but not limited to, excessive lung inflammation and increased susceptibility to infection. Therefore, the overall objective of this study was to examine the effects of statins on CFassociated bacterial pathogens and the host response. In this work, the prevalence of HMGR was examined in respiratory pathogens, and several CF-associated pathogens were found to possess homologues of this enzyme. HMGR homology was analysed in Staphylococcus aureus, Burkholderia cenocepacia and Streptococcus pneumoniae, and the HMGR of B. cenocepacia was found to have significant conservation to that of Pseudomonas mevalonii, which is the most widely-characterised bacterial HMGR. However, in silico analysis revealed that, unlike S. aureus and S. pneumoniae, B. cenocepacia did not possess homologues of other mevalonate pathway proteins, and that the HMGR of B. cenocepacia appeared to be involved in an alternative metabolic pathway. The effect of simvastatin was subsequently tested on the growth and virulence of S. aureus, B. cenocepacia and S. pneumoniae. Simvastatin inhibited the growth of all 3 species in a dose-dependent manner. In addition, statin treatment also attenuated biofilm formation of all 3 species, and reduced in vitro motility of S. aureus. Interestingly, simvastatin also increased the potency of the aminoglycoside antibiotic gentamicin against B. cenocepacia. The impact of statins was subsequently tested on the predominant CF-associated pathogen Pseudomonas aeruginosa, which does not possess a HMGR homologue. Mevastatin, lovastatin and simvastatin did not influence the growth of this species. However, sub-inhibitory statin concentrations reduced the swarming motility and biofilm formation of P. aeruginosa. The influence of statins was also examined on Type 3 toxin secretion, quorum sensing and chemotaxis, and no statin effect was observed on any of these phenotypes. Statins did not appear to have a characteristic effect on the P. aeruginosa transcriptome. However, a mutant library screen revealed that the effect of statins on P. aeruginosa biofilm was mediated through the PvrR regulator and the Cup fimbrial biosynthesis genes. Furthermore, proteomic analysis demonstrated that 6 proteins were reproducibly induced by simvastatin in the P. aeruginosa swarming cells. The effect of statins on the regulation of the host-P. aeruginosa immune response was also investigated. Statin treatment increased expression of the pro-inflammatory cytokines IL-8 and CCL20 in lung epithelial cells, but did not attenuate P. aeruginosa-mediated inflammatory gene induction. In fact, simvastatin and P. aeruginosa caused a synergistic effect on CCL20 expression. The expression of the transcriptional regulators KLF2 and KLF6 was also increased by statins and P. aeruginosa, with the induction of KLF6 by simvastatin proving to be a novel effect. Interestingly, both statins and P. aeruginosa were capable of inducing alternative splicing of KLF6. P. aeruginosa was found to induce KLF6 alternative splicing by way of the type 3 secreted toxin ExoS. In addition, a mechanistic role was elucidated for KLF6 in the lung, as it was determined that statin-mediated induction of this protein was responsible for the induction of the host response genes CCL20 and iNOS. Moreover, statin treatment caused a slight increase in infection-related cytotoxicity, and increased bacterial adhesion to cells. Taken together, these data demonstrate that statins can reduce the virulence of CFassociated bacterial pathogens and alter host response effectors. Furthermore, novel statin effectors were identified in both bacterial and host cells.

Post-cesarean Section Peritonitis at a Referral Hospital in Rwanda: Factors Associated with Maternal Morbidity and Mortality

Background: Post-cesarean section peritonitis is the leading cause of maternal morbidity and mortality at the main referral hospital in Rwanda. Published data on the management of post-cesarean section peritonitis is limited. This study examined predictors of maternal morbidity and mortality for post-cesarean peritonitis.

Methods: We performed a prospective observational cohort study at the University Teaching Hospital Kigali (CHUK) from January 1 until December 31 2015, followed by a retrospective chart review of all subjects with post-cesarean section peritonitis admitted to CHUK from January 1 until December 31, 2014. All patients admitted with the diagnosis of post-cesarean section peritonitis undergoing exploratory laparotomy at CHUK were enrolled. Patients were followed to either discharge or death. Study variables included baseline demographic/clinical characteristics, admission physical exam, intraoperative findings, and management. Data were analyzed using STATA version 14.

Results: Of the 167 patients enrolled, 81 survived without requiring hysterectomy (49%), 49 survived requiring hysterectomy (29%), and 36 died (22%). In the multivariate analysis, severe sepsis was the most significant predictor of mortality (RR=4.0 [2.2-7.7]) and uterine necrosis was the most significant predictor of hysterectomy (RR=6.3 [1.6-25.2]). There were high rates of antimicrobial resistance (AMR) among the bacterial isolates cultured from intra-abdominal pus, with 52% of bacteria resistant to third-generation cephalosporins.

Conclusions: Post-cesarean section peritonitis carries a high mortality rate in Rwanda. It is also associated with a high rate of hysterectomy. Understanding the disease process and identifying factors associated with outcomes can help guide management during admission.