967 resultados para Catheter-related bloodstream infection


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Aim: To develop and evaluate a rapid enzyme linked immunosorbent assay (ELISA) for the diagnosis of intravascular catheter related sepsis caused by coagulase negative staphylococci. Methods: Forty patients with a clinical and microbiological diagnosis of intravascular catheter related sepsis and positive blood cultures, caused by coagulase negative staphylococci, and 40 control patients requiring a central venous catheter as part of their clinical management were recruited into the study. Serum IgG responses to a previously undetected exocellular antigen produced by coagulase negative staphylococci, termed lipid S, were determined in the patient groups by a rapid ELISA. Results: There was a significant difference (p = < 0.0001) in serum IgG to lipid S between patients with catheter related sepsis and controls. The mean antibody titre in patients with sepsis caused by coagulase negative staphylococci was 10 429 (range, no detectable serum IgG antibody to 99 939), whereas serum IgG was not detected in the control group of patients. Conclusions: The rapid ELISA offers a simple, economical, and rapid diagnostic test for suspected intravascular catheter related sepsis caused by coagulase negative staphylococci, which can be difficult to diagnose clinically. This may facilitate treatment with appropriate antimicrobials and may help prevent the unnecessary removal of intravascular catheters.

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INTRODUÇÃO: As infecções de corrente sanguínea relacionadas com cateter (ICSRCs) apresentam impacto significativo na morbidade e na mortalidade de pacientes internados, além de elevar custos hospitalares. A utilização de equipamentos automatizados no processamento de hemoculturas gerou uma alternativa para diagnóstico de ICSRC por meio da análise da diferença de tempo de positividade (DTP) entre hemoculturas pareadas (coletadas simultaneamente) de sangue periférico e sangue de cateter. Um diagnóstico acurado e rápido dessas infecções pode otimizar as condutas clínicas e terapêuticas, poupando a retirada precoce dos cateteres. OBJETIVOS: Avaliar na rotina a DTP como ferramenta auxiliar no diagnóstico de ICSRC e determinar os principais microrganismos isolados. MÉTODOS: Foram avaliadas retrospectivamente hemoculturas coletadas no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP) de maio a agosto de 2008. Somente amostras que apresentaram DTP maior que 120 minutos foram consideradas possíveis ICSRCs pelo critério laboratorial. RESULTADOS: A seção processou 11.017 hemoculturas aeróbias durante o período de estudo; somente 5% foram coletadas de forma pareada. Destas, 148 (28%) foram positivas, sendo 9% com crescimento somente em sangue periférico, 41% somente em sangue de cateter e 50% em ambas as amostras com 88% de homologia de microrganismos identificados. A DTP apresentou valores acima de 120 minutos em 50% dos casos e os microrganismos mais isolados foram Staphylococcus aureus (22%), Candida spp. (18%), Klebsiella spp. (7%) e Enterobacter spp. (7%). CONCLUSÃO: A determinação da DTP como ferramenta auxiliar no diagnóstico de ICSRC é viável e fácil de ser executada em laboratórios de rotina com automação, porém o processo de coleta das amostras pareadas deve ser rigidamente padronizado.

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BACKGROUND Although superficial thrombophlebitis of the upper extremity represents a frequent complication of intravenous catheters inserted into the peripheral veins of the forearm or hand, no consensus exists on the optimal management of this condition in clinical practice. OBJECTIVES To summarise the evidence from randomised clinical trials (RCTs) concerning the efficacy and safety of (topical, oral or parenteral) medical therapy of superficial thrombophlebitis of the upper extremity. SEARCH METHODS The Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). Clinical trials registries were searched up to April 2015. SELECTION CRITERIA RCTs comparing any (topical, oral or parenteral) medical treatment to no intervention or placebo, or comparing two different medical interventions (e.g. a different variant scheme or regimen of the same intervention or a different pharmacological type of treatment). DATA COLLECTION AND ANALYSIS We extracted data on methodological quality, patient characteristics, interventions and outcomes, including improvement of signs and symptoms as the primary effectiveness outcome, and number of participants experiencing side effects of the study treatments as the primary safety outcome. MAIN RESULTS We identified 13 studies (917 participants). The evaluated treatment modalities consisted of a topical treatment (11 studies), an oral treatment (2 studies) and a parenteral treatment (2 studies). Seven studies used a placebo or no intervention control group, whereas all others also or solely compared active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, the risk of bias in individual trials was moderate to high, although poor reporting hampered a full appreciation of the risk in most studies. The overall quality of the evidence for each of the outcomes varied from low to moderate mainly due to risk of bias and imprecision, with only single trials contributing to most comparisons. Data on primary outcomes improvement of signs and symptoms and side effects attributed to the study treatment could not be statistically pooled because of the between-study differences in comparisons, outcomes and type of instruments to measure outcomes.An array of topical treatments, such as heparinoid or diclofenac gels, improved pain compared to placebo or no intervention. Compared to placebo, oral non-steroidal anti-inflammatory drugs reduced signs and symptoms intensity. Safety issues were reported sparsely and were not available for some interventions, such as notoginseny creams, parenteral low-molecular-weight heparin or defibrotide. Although several trials reported on adverse events with topical heparinoid creams, Essaven gel or phlebolan versus control, the trials were underpowered to adequately measure any differences between treatment modalities. Where reported, adverse events with topical treatments consisted mainly of local allergic reactions. Only one study of 15 participants assessed thrombus extension and symptomatic venous thromboembolism with either oral non-steroidal anti-inflammatory drugs or low-molecular-weight heparin, and it reported no cases of either. No study reported on the development of suppurative phlebitis, catheter-related bloodstream infections or quality of life. AUTHORS' CONCLUSIONS The evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality. Data appear too preliminary to assess the effectiveness and safety of topical treatments, systemic anticoagulation or oral non-steroidal anti-inflammatory drugs.

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Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important pathogens of nosocomial infections, mainly in intensive care units (ICUs), and accounts for 40-60% of all healthcare-associated S. aureus infections. We evaluated the incidence of nosocomial infection by S. aureus, identified the risk factors for MRSA infection, and evaluated the effect of resistance to methicillin on mortality in patients. Methods We conducted MRSA surveillance at a university hospital in Brazil from January 1, 2010, to December 31, 2010, and performed a retrospective case-control matched study to evaluate the frequency of subsequent MRSA bacteremia and death among patients. We evaluated and compared the risk factors between patients with MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) infection. Results Sepsis was the most common cause of infection (17.7/1,000 patient-days), followed by surgical site (11.4/1,000 patient-days), pneumonia (4.1/1,000 patient-days), and urinary tract infection (2.4/1,000 patient-days). The significant risk factors were time of hospitalization, use of central vascular catheter (CVC), urinary catheter, nasogastric tube, parenteral nutrition, tracheostomy, mechanical ventilation, and previous antibiotic administration, the latter of which was the only independent risk factor for MRSA infection. Mortality was significantly higher in patients with MRSA. The number of antibiotics tested was not related to increases in the frequency of MRSA/1,000 patient-days. The incidence of mortality attributable to MRSA (bloodstream infection) BSI was 50%. Conclusions Surveillance results showed that the use of high levels of antibiotics was directly related to the development of MRSA infection, and the mortality attributable to MRSA in patients with bacteremia was significant.

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OBJECTIVES: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING: EPIC II included 1265 intensive care units in 76 countries. PATIENTS: Patients in participating intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.

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Catheter-related bacteremia (CRB) is one of the various complications related to hemodialysis (HD). As a result of this high rate of infection, the antibiotic lock technique (ALT) has been recommended to prevent CRB. However, adverse effects of ALT such as increased emergence of strains resistant to antibiotics and increased mechanical dysfunction catheter were poorly evaluated. We prospectively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB. A total of 233 HD patients requiring 325 new tunneled catheters while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study. Patients with a tunneled catheter were assigned to receive either an antibiotic-heparin lock solution (antibiotic group: cefazolin 10 mg/ml, gentamicin 5 mg/ml, heparin 1,000 U/ml) or a heparin lock solution (no-antibiotic group: heparin 1,000 U/ml) as a catheter lock solution during the interdialytic period. The present study aimed to assess the efficacy of ALT using cefazolin and gentamicin in reducing CRB in patients undergoing HD with tunneled central catheter and to identify its adverse effects. CRB developed in 32.4 % of patients in the no-antibiotic group and in 13.1 % of patients in the antibiotic group. CRB rates per 1,000 catheter-days were 0.57 in the antibiotic group versus 1.74 in the no-antibiotic group (p < 0.0001). Kaplan-Meier analysis also showed that mean CRB-free catheter survival was significantly higher in the antibiotic group than in the no-antibiotic group (log-rank statistic 17.62, p < 0.0001). There was statistically significant difference between the two groups in causative organisms of CRB, with predominance of negative culture in both groups, but this prevalence was higher in ALT group (57.9 vs 90.1 %, p < 0.0001), and the two groups also were different in prevalence of gram-positive bacteria as causing organisms (ALT group 21.05 vs = 0 % in control group, p < 0.0001). There was no statistically significant difference between the two groups in drug-resistant germs. There were statistically significant differences between the two groups in the catheter removal causes, with higher rate of infectious cause in control group (12.32 vs 2.22 %, p < 0.0001) and mechanical cause in ALT group (28.26 vs 37.78 %, p < 0.0001). The results suggest that ALT may be a beneficial means of reducing the CRB rate in HD patients with tunneled catheter, without association between ALT and emergence of strains resistant. However, mechanical complications were more prevalent in antibiotic group. Further studies are required to determine the optimal drug regimen, concentrations for ALT, and its adverse effects. © 2012 Springer Science+Business Media Dordrecht.

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Central venous catheters (CVCs) are being utilized with increasing frequency in intensive care and general medical wards. In spite of the extensive experience gained in their application, CVCs are related to the long-term risks of catheter sheath formation, infection, and thrombosis (of the catheter or vessel itself) during catheterization. Such CVC-related-complications are associated with increased morbidity, mortality, duration of hospitalization, and medical care cost [1]. The present study incorporates a novel group of Factor XIIIa (FXIIIa, plasma transglutaminase) inhibitors into a lubricious silicone elastomer in order to generate an optimized drug delivery system whereby a secondary sustained drug release profile occurs following an initial burst release for catheters and other medical devices. We propose that the incorporation of FXIIIa inhibitors into catheters, stents, and other medical implant devices would reduce the incidence of catheter sheath formation, thrombotic occlusion, and associated staphylococcal infection. This technique could be used as a local delivery system for extended release with an immediate onset of action for other poorly aqueous soluble compounds. © 2012 Elsevier B.V. All rights reserved.

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2000 Mathematics Subject Classification: 62J12, 62P10.

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Governmental programmes should be developed to collect and analyse data on healthcare associated infections (HAIs). This study describes the healthcare setting and both the implementation and preliminary results of the Programme for Surveillance of Healthcare Associated Infections in the State of Sao Paulo (PSHAISP), Brazil, from 2004 to 2006. Characterisation of the healthcare settings was carried out using a national database. The PSHAISP was implemented using components for acute care hospitals (ACH) or long term care facilities (LTCF). The components for surveillance in ACHs were surgical unit, intensive care unit and high risk nursery. The infections included in the surveillance were surgical site infection in clean surgery, pneumonia, urinary tract infection and device-associated bloodstream infections. Regarding the LTCF component, pneumonia, scabies and gastroenteritis in all inpatients were reported. In the first year of the programme there were 457 participating healthcare settings, representing 51.1% of the hospitals registered in the national database. Data obtained in this study are the initial results and have already been used for education in both surveillance and the prevention of HAI. The results of the PSHAISP show that it is feasible to collect data from a large number of hospitals. This will assist the State of Sao Paulo in assessing the impact of interventions and in resource allocation. (C) 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

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OBJECTIVE. To identify risk factors associated with nosocomial bloodstream infections caused by multiple clones of the staphylococcal cassette chromosome mec (SCCmec) type IV strain of methicillin-resistant Staphylococcus aureus (MRSA). DESIGN. An unmatched case-control study (at a ratio of 1 : 2) performed during the period from October 2002 through September 2003. SETTING. A 2,000-bed tertiary care teaching hospital affiliated with the University of Sao Paulo in Sao Paulo, Brazil. METHODS. Case patients (n = 30) were defined either as patients who had a bloodstream infection due to SCCmec type IV strains of MRSA diagnosed at least 48 hours after hospital admission or as neonates with the infection who were born in the hospital. Control patients (n = 60) were defined as patients with SCCmec type III MRSA infection diagnosed at least 48 hours after hospital admission. Genes n = 60 encoding virulence factors were studied in the isolates recovered from case patients, and molecular typing of the SCCmec type IV MRSA isolates was also done by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS. In multivariate analysis, the following 3 variables were significantly associated with having a nosocomial bloodstream infection caused by SCCmec type IV strains of MRSA: an age of less than 1 year, less frequent use of a central venous catheter (odds ratio [OR], 0.07 [95% confidence interval {CI}, 0.02-0.28]; P = .001), and female sex. A second analysis was performed that excluded the case and Pp. 001 control patients from the neonatal unit, and, in multivariate analysis, the following variables were significantly associated with having a nosocomial bloodstream infection caused by SCCmec type IV strains of MRSA: less frequent use of a central venous catheter (OR, 0.12 [95% CI, 0.03-0.55]; P = .007), lower Acute Physiology and Chronic Health Evaluation II score on admission (OR, 0.14 [95% CI, 0.03-0.61];), less frequent surgery (OR, 0.21 [95% CI, 0.06-0.83];), and female sex (OR, 5.70 [95% CI, 1.32-24.66]; P =.020). P = .009 Pp. 025 Pp). Of the 29 SCCmec type IV MRSA isolates recovered from case patients, none contained the Panton-Valentine leukocidin, gamma-hemolysin, enterotoxin B or C, or toxic shock syndrome toxin-1. All of the isolates contained genes for the LukE-LukD leukocidin and alpha-hemolysin. Genes for enterotoxin A were present in 1 isolate, and genes for beta-hemolysin were present in 3 isolates. CONCLUSIONS. ""Classical"" risk factors do not apply to patients infected with the SCCmec type IV strain of MRSA, which is an important cause of nosocomial bacteremia. This strain infects a patient population that is less ill and has had less frequent invasive procedures than a patient population infected with the multidrug-resistant strain of SCCmec type III MRSA. We found that virulence factors were rare and that Panton-Valentine leukocidin was absent. There were multiple clones of the SCCmec type IV strain in our hospital. Children under 1 year of age were at a higher risk. There was a predominant clone ( sequence type 5) in this patient population.

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objective. To describe the management of patients with long-term central venous catheters (CVCs) during an outbreak of infection due to Pseudomonas putida and Stenotrophomonas maltophilia associated with contaminated heparin catheter-lock solution. design. Descriptive study. setting. Private, 250-bed tertiary-care hospital. methods. In March 2003, we identified 2 febrile cancer patients with P. putida bacteremia. Over 2 days, 7 cases of bacteremia were identified; lots of syringes prefilled with heparin catheter-lock solution, supplied by a compounding pharmacy, were recalled and samples were cultured. More cases of bacteremia appeared during the following days, and any patient who had had a catheter lock infused with the suspect solution was asked to provide blood samples for culture, even if the patient was asymptomatic. Isolates that were recovered from culture were typed by pulsed-field gel electrophoresis. Antimicrobial salvage treatment of long-term CVCs was attempted. results. A total of 154 patients had had their catheter lock infused with solution from the lots that were suspected of being contaminated. Only 48 of these patients had CVCs. By day 7 of the outbreak, 18 of these patients had become symptomatic. Twenty-six of the remaining 30 asymptomatic patients then also provided blood samples for culture, 10 of whom developed fever shortly after samples were collected. Thirty-two patients were identified who had P. putida bacteremia; 9 also had infection due to S. maltophilia. Samples from 1 of the 3 lots of prefilled syringes in use at the time of the outbreak also grew P. putida on culture. Molecular typing identified 3 different clones of P. putida from patients and heparin catheter-lock solution, and 1 clone of S. maltophilia. A total of 27 patients received antimicrobial therapy regimens, some of which included decontamination of the catheter lock with anti- infective lock solution. Of 27 patients, 19 (70%) retained their long-term CVC during the 6-month follow-up period. conclusions. To our knowledge, this is one of the largest prospective experiences in the management of bloodstream infection associated with long-term CVCs. The infections were caused by gram-negative bacilli and were managed without catheter removal, with a high response rate. We emphasize the risks of using intravenous formulations of medications supplied by compounding pharmacies that produce large quantities of drugs.

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Parenteral nutrition therapy is used in patients with a contraindication to the use of the gastrointestinal tract, and infection is one of its Frequent and severe complications. The objective of the present study was to detect the presence of biofilms and microorganisms adhering to the central venous. catheters used for parenteral nutrition therapy by scanning electron microscopy. Thirty-nine central venous catheters belonging to patients with clinical signs of infection (G I) and asymptomatic patients (G2) and patients receiving central venous catheters for clinical monitoring (G3) were analyzed by semi-quantitative culture and scanning electron microscopy. The central venous catheters of G1 presented more positive cultures than those of G2 and G3 (81% vs 50% and 0%, respectively). However, biofilms were observed in all catheters used and 55% of them showed structures that suggested central venous catheters colonization by microorganisms. Approximately 53% of the catheter infections evolved with systemic infection confirmed by blood Culture. The authors conclude that the presence of a biofilm is frequent and is all indicator of predisposition to infection, which may even occur in patients who are still asymptomatic. (JPEN J Parenter Enteral Nutr. 2009;33:397-403)

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This study reports on a block clinical trial of two types of central venous catheters (CVCs): antiseptic-impregnated catheters (AIC) and non-impregnated catheters (non-AIC), on catheter tip colonization and bacteraemia. In total, 500 catheters were inserted in 390 patients over the 18 month study period, 260 (52.0%) AIC and 240 (48.0%) non-AIC. Of these, 460 (92.0%) tips (237 AIC and 223 non-AIC) were collected. While significantly fewer AIC, 14 (5.9%), than non-AIC, 30 (13.5%), catheters were colonized (P < 0.01), there was no difference in the rates of bacteraemias in the two groups (0.8% vs. 2.7%, respectively, P = 0.16). There were 6.87 (95% CI 3.38-14.26) and 16.92 (95% CI 10.61-27.12) colonized AIC and non-AIC catheters, respectively, per 1000 catheter days, a difference that was significant (P < 0.01). However, no difference emerged between bacteraemias in AIC and non-AIC catheters per 1000 catheter days measured at 0.98 (95% CI 0.24-5.54) and 3.38 (95% CI 1.29-9.34), respectively (P = 0.10). Of the 444 CVCs that were sited in the subclavian or jugular veins and had tips collected, significantly more catheters were colonized in the jugular group, 19 (20%), compared with the subclavian group, 24 (6.9%; P less than or equal to 0.01). Overall, the low rates of colonization and bacteraemia may be explained by the population studied, the policies used and the employment of a clinical nurse dedicated to CVC management. (C) 2003 The Hospital Infection Society. Published by Elsevier Science Ltd. All rights reserved.

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Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc) in bone marrow transplant and hematology outpatients.Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW) hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC) care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units.Findings: 14 patients had B. multivorans(one patient had also B. cenopacia), six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology); in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30%) were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication), no new cases occurred.Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A) of multi-dose vials.

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RESUMO - Introdução: As Infeções nosocomiais da corrente sanguínea associada a cateter venoso central (INCS-CVC) provocam um aumento das despesas hospitalares, traduzindo num aumento dos dias de internamento, consumo de antibióticos e de meios complementares de diagnóstico e terapêutica (MCDT). O presente estudo pretende avaliar os custos das INCS-CVC nos serviços de internamento do CHLO, no ano de 2012. Metodologia: Realizou-se um estudo retrospetivo de caso-controlo para determinar os custos adicionais inerentes às INCS-CVC. Foram identificados, em 2012, 32 doentes com infeção e 31 sem infeção. Os controlos foram extraídos da população tendo igual grupo diagnóstico Homogéneo (GDH), idade, sexo, serviço e duração de internamento e presença de CVC. As principais fontes de informação foram os registos da Comissão Controlo de Infeção (CCI) e do processo clinico eletrónico (PCE). A estimativa dos custos teve em consideração a duração de internamento, consumo de antibióticos e de MCDT. Resultados: A idade média dos casos e controlos foi de 66 e 69, respetivamente (p=0,432), 50% dos casos e 51,6% dos controlos eram do sexo masculino. Um total de 22 casos foi comparado com 22 controlos. A duração média de internamento dos casos e controlos foi de 70,8 e 36,6 dias, respetivamente (p=0,000). Em média o custo adicional por doente com antibióticos foi de 256€ (p=0,001). Nos casos o consumo de análises clinica foi 2,5 vezes superior e de exames imagiológicos 2 vezes superior aos controlos. O custo total médio adicional por doente foi de 20.737,6€. Conclusão: A ocorrência de INCS-CVC resultou num aumento significativo de utilização de recursos hospitalares e consequentemente num aumento dos custos hospitalares.