Adenosinergic System and BDNF Signaling Changes as a Cross-Sectional Feature of RTT: Characterization of Mecp2 Heterozygous Mouse Females.

Rett Syndrome is an X-linked neurodevelopmental disorder (RTT; OMIM#312750) associated to MECP2 mutations. MeCP2 dysfunction is seen as one cause for the deficiencies found in brain-derived neurotrophic factor (BDNF) signaling, since BDNF is one of the genes under MeCP2 jurisdiction. BDNF signaling is also dependent on the proper function of the adenosinergic system. Indeed, both BDNF signaling and the adenosinergic system are altered in Mecp2-null mice (Mecp2-/y), a representative model of severe manifestation of RTT. Considering that symptoms severity largely differs among RTT patients, we set out to investigate the BDNF and ADO signaling modifications in Mecp2 heterozygous female mice (Mecp2+/-) presenting a less severe phenotype. Symptomatic Mecp2+/- mice have lower BDNF levels in the cortex and hippocampus. This is accompanied by a loss of BDNF-induced facilitation of hippocampal long-term potentiation (LTP), which could be restored upon selective activation of adenosine A2A receptors (A2AR). While no differences were observed in the amount of adenosine in the cortex and hippocampus of Mecp2+/- mice compared with healthy littermates, the density of the A1R and A2AR subtype receptors was, respectively, upregulated and downregulated in the hippocampus. Data suggest that significant changes in BDNF and adenosine signaling pathways are present in an RTT model with a milder disease phenotype: Mecp2+/- female animals. These features strengthen the theory that boosting adenosinergic activity may be a valid therapeutic strategy for RTT patients, regardless of their genetic penetrance.

Impairment of adenosinergic system in Rett syndrome: Novel therapeutic target to boost BDNF signalling.

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.

Identification of hospitalized patients with community-acquired infection in whom treatment guidelines do not apply: a validated model.

OBJECTIVES: To develop and validate a clinical model to identify patients admitted to hospital with community-acquired infection (CAI) caused by pathogens resistant to antimicrobials recommended in current CAI treatment guidelines. METHODS: International prospective cohort study of consecutive patients admitted with bacterial infection. Logistic regression was used to associate risk factors with infection by a resistant organism. The final model was validated in an independent cohort. RESULTS: There were 527 patients in the derivation and 89 in the validation cohort. Independent risk factors identified were: atherosclerosis with functional impairment (Karnofsky index <70) [adjusted OR (aOR) (95% CI) = 2.19 (1.41-3.40)]; previous invasive procedures [adjusted OR (95% CI) = 1.98 (1.28-3.05)]; previous colonization with an MDR organism (MDRO) [aOR (95% CI) = 2.67 (1.48-4.81)]; and previous antimicrobial therapy [aOR (95% CI) = 2.81 (1.81-4.38)]. The area under the receiver operating characteristics (AU-ROC) curve (95% CI) for the final model was 0.75 (0.70-0.79). For a predicted probability ≥22% the sensitivity of the model was 82%, with a negative predictive value of 85%. In the validation cohort the sensitivity of the model was 96%. Using this model, unnecessary broad-spectrum therapy would be recommended in 30% of cases whereas undertreatment would occur in only 6% of cases. CONCLUSIONS: For patients hospitalized with CAI and none of the following risk factors: atherosclerosis with functional impairment; previous invasive procedures; antimicrobial therapy; or MDRO colonization, CAI guidelines can safely be applied. Whereas, for those with some of these risk factors, particularly if more than one, alternative antimicrobial regimens should be considered.

Intra-abdominal infections: the role of different classifications on the selection of the best antibiotic treatment.

BACKGROUND: Intra-abdominal infections (IAIs) represent a most frequent gastrointestinal emergency and serious cause of morbimortality. A full classification, including all facets of IAIs, does not exist. Two classifications are used to subdivide IAIs: uncomplicated or complicated, considering infection extent; and community-acquired, healthcare-associated or hospital-acquired, regarding the place of acquisition. Adequacy of initial empirical antibiotic therapy prescribed is an essential need. Inadequate antibiotic therapy is associated with treatment failure and increased mortality. This study was designed to determine accuracy of different classifications of IAIs to identify infections by pathogens sensitive to current treatment guidelines helping the selection of the best antibiotic therapy. METHODS: A retrospective cohort study including all adult patients discharged from hospital with a diagnosis of IAI between 1st of January and 31st of October, 2016. All variables potentially associated with pre-defined outcomes: infection by a pathogen sensitive to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (ATB 1, primary outcome), sensitive to piperacillin-tazobactam (ATB 2) and hospital mortality (secondary outcomes) were studied through logistic regression. Accuracy of the models was assessed by area under receiver operating characteristics (AUROC) curve and calibration was tested using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Of 1804 patients screened 154 met inclusion criteria. Sensitivity to ATB 1 was independently associated with male gender (adjusted OR = 2.612) and previous invasive procedures in the last year (adjusted OR = 0.424) (AUROC curve = 0,65). Sensitivity to ATB 2 was independently associated with liver disease (adjusted OR = 3.580) and post-operative infections (adjusted OR = 2.944) (AUROC curve = 0.604). Hospital mortality was independently associated with age ≥ 70 (adjusted OR = 4.677), solid tumour (adjusted OR = 3.127) and sensitivity to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (adjusted OR = 0.368). The accuracy of pre-existing classifications to identify infection by a pathogen sensitive to ATB 1 was 0.59 considering place of acquisition, 0.61 infection extent and 0.57 local of infection, for ATB 2 it was 0.66, 0.50 and 0.57, respectively. CONCLUSION: None of existing classifications had a good discriminating power to identify IAIs caused by pathogens sensitive to current antibiotic treatment recommendations. A new classification, including patients' individual characteristics like those included in the current model, might have a higher potential to distinguish IAIs by resistant pathogens allowing a better choice of empiric antibiotic therapy.

Microbiology of healthcare-associated infections and the definition accuracy to predict infection by potentially drug resistant pathogens: a systematic review.

BACKGROUND: Healthcare-associated infections (HCAI) represent up to 50 % of all infections among patients admitted from the community. The current review intends to provide a systematic review on the microbiological profile involved in HCAI, to compare it with community-acquired (CAI) and hospital-acquired infections (HAI) and to evaluate the definition accuracy to predict infection by potentially drug resistant pathogens. METHODS: We search for HCAI in MEDLINE, SCOPUS and ISI Web of Knowledge with no limitations in regards to publication language, date of publication, study design or study quality. Only studies using the definition by Friedman et al. were included. This review was registered at PROSPERO Systematic Review Registration with the Number CRD42014013648. RESULTS: A total of 21 eligible studies with 12,096 infected patients were reviewed; of these 3497 had HCAI, 2723 were microbiologically documented. Twelve studies were on pneumonia involving 1051 patients with microbiological documented HCAI, the application of the current guidelines for this group of patients would result in an appropriate antibiotic therapy in 95 % of cases at the expense of overtreatment in 73 %; the application of community-acquired pneumonia guidelines would be adequate in only 73-76 % of the cases; an alternative regimen with piperacillin-tazobactam or aztreonam plus azithromycin would increase antibiotic adequacy rate to 90 %. Few studies were found on additional focus of infection: endocarditis, urinary, intra-abdominal and bloodstream infections. All studies included in this review showed an association of the HCAI definition with infection by PDR pathogens when compared to CAI [odds ratio (OR) 4.05, 95 % confidence interval (95 % CI) 2.60-6.31)]. The sensitivity of HCAI to predict infection by a PDR pathogen was 0.69 (0.65-0.72), specificity was 0.67 (0.66-0.68), positive likelihood ratio was 1.9 and the area under the summary ROC curve was 0.71. CONCLUSIONS: This systematic review provides evidence that HCAI represents a separate group of infections in terms of the microbiology profile, including a significant association with infection by PDR pathogens, for the main focus of infection. The results provided can help clinician in the selection of empiric antibiotic therapy and international societies in the development of specific treatment recommendations.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes.

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting. METHODS: An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. RESULTS: A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis. CONCLUSIONS: IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.

Classification of healthcare-associated infection: a systematic review 10 years after the first proposal.

BACKGROUND: Ten years after the first proposal, a consensus definition of healthcare-associated infection (HCAI) has not been reached, preventing the development of specific treatment recommendations. A systematic review of all definitions of HCAI used in clinical studies is made. METHODS: The search strategy focused on an HCAI definition. MEDLINE, SCOPUS and ISI Web of Knowledge were searched for articles published from earliest achievable data until November 2012. Abstracts from scientific meetings were searched for relevant abstracts along with a manual search of references from reports, earlier reviews and retrieved studies. RESULTS: The search retrieved 49,405 references: 15,311 were duplicates and 33,828 were excluded based on title and abstract. Of the remaining 266, 43 met the inclusion criteria. The definition more frequently used was the initial proposed in 2002--in infection present at hospital admission or within 48 hours of admission in patients that fulfilled any of the following criteria: received intravenous therapy at home, wound care or specialized nursing care in the previous 30 days; attended a hospital or hemodialysis clinic or received intravenous chemotherapy in the previous 30 days; were hospitalized in an acute care hospital for ≥2 days in the previous 90 days, resided in a nursing home or long-term care facility. Additional criteria founded in other studies were: immunosuppression, active or metastatic cancer, previous radiation therapy, transfer from another care facility, elderly or physically disabled persons who need healthcare, previous submission to invasive procedures, surgery performed in the last 180 days, family member with a multi-drug resistant microorganism and recent treatment with antibiotics. CONCLUSIONS: Based on the evidence gathered we conclude that the definition initially proposed is widely accepted. In a future revision, recent invasive procedures, hospitalization in the last year or previous antibiotic treatment should be considered for inclusion in the definition. The role of immunosuppression in the definition of HCAI still requires ongoing discussion.

Mentha piperita essential oil induces apoptosis in yeast associated with both cytosolic and mitochondrial ROS-mediated damage.

Mentha piperita (MP), also known as peppermint, is an aromatic and medicinal plant widely used in the food industry, perfumery and cosmetic, pharmacy and traditional medicine. Its essential oil (EO) displays antimicrobial activity against a range of bacteria and fungi. In this study, we found that MP EO lethal cytotoxicity is associated with increased levels of intracellular reactive oxygen species, mitochondrial fragmentation and chromatin condensation, without loss of the plasma membrane integrity, indicative of an apoptotic process. Overexpression of cytosolic catalase and superoxide dismutases reverted the lethal effects of the EO and of its major component menthol. Conversely, deficiency in Sod1p (cytosolic copper-zinc-superoxide dismutase) greatly increased sensitivity to both agents, but deficiency in Sod2p (mitochondrial manganese superoxide dismutase) only induced sensitivity under respiratory growth conditions. Mentha piperita EO increased the frequency of respiratory deficient mutants indicative of damage to the mitochondrial genome, although increase in mitochondrial thiol oxidation does not seem to be involved in the EO toxicity.

Purinergic modulation of norepinephrine release and uptake in rat brain cortex: contribution of glial cells.

The pathogenesis of psychiatric and neurodegenerative diseases is often associated with a deregulation of noradrenergic transmission. Considering the potential involvement of purinergic signaling in the modulation of noradrenergic transmission in the brain cortex, this study aimed to identify the P2Y receptor subtypes involved in the modulation of neuronal release and neuronal/glial uptake of norepinephrine. Electrical stimulation (100 pulses at 5 Hz) of rat cortical slices induced norepinephrine release that was inhibited by ATP and ADP (0.01-1 mM), adenosine 5'-O-(2-thiodiphosphate) (ADPßS, 0.03-0.3 mM), and UDP (0.1-1 mM). The effect of ADPßS was mediated by P2Y1 receptors and possibly by A1/P2Y1 heterodimers since it was attenuated by the A1 receptor antagonist DPCPX and by the P2Y1 receptor antagonist MRS 2500 but was resistant to the effect of adenosine deaminase (ADA). UDP inhibited norepinephrine release through activation of P2Y6 receptors, an effect that was abolished by the P2Y6 receptor antagonist MRS 2578 and by DPCPX, indicating that it depends on the formation and/or release of adenosine and activation of A1 receptors. Supporting this hypothesis, the inhibitory effect of UDP was also prevented by inhibition of ectonucleotidases, by ADA and was attenuated by the inhibitor of nucleoside transporter 6-[(4-nitrobenzyl)thio]-9-ß-d-ribofuranosylpurine (NBTI). Additionally, the inhibitory effect of UDP was attenuated when norepinephrine uptake 1 or 2 was inhibited. In astroglial cultures, ADPßS and UDP increased norepinephrine uptake mainly by activation of P2Y1 and P2Y6 receptors, respectively. The results indicate that neuronal and glial P2Y1 and P2Y6 receptors may represent new targets of intervention to regulate noradrenergic transmission in CNS diseases.

Differences in compliance with Surviving Sepsis Campaign recommendations according to hospital entrance time: day versus night.

INTRODUCTION: Higher compliance with Surviving Sepsis Campaign (SSC) recommendations has been associated with lower mortality. The authors evaluate differences in compliance with SSC 6-hour bundle according to hospital entrance time (day versus night) and its impact on hospital mortality. METHODS: Prospective cohort study of all patients with community-acquired severe sepsis admitted to the intensive care unit of a large university tertiary care hospital, over 3.5 years with a follow-up until hospital discharge. Time to compliance with each recommendation of the SSC 6-hour bundle was calculated according to hospital entrance period: day (08:30 to 20:30) versus night (20:30 to 08:30). For the same periods, clinical staff composition and the number of patients attending the emergency department (ED) was also recorded. RESULTS: In this period 300 consecutive patients were included. Compliance rate was (night vs. day): serum lactate measurement 57% vs. 49% (P = 0.171), blood cultures drawn 59% vs. 37% (P < 0.001), antibiotics administration in the first 3 hours 33% vs. 18% (P = 0.003), central venous pressure >8 mmHg 45% vs. 29% (P = 0.021), and central venous oxygen saturation (SvcO2) >70%, 7% vs. 2% (P = 0.082); fluids were administered in all patients with hypotension in both periods and vasopressors were administered in patients with hypotension not responsive to fluids in 100% vs. 99%. Time to get specific actions done was also different (night vs. day): serum lactate measurement (4.5 vs. 7 h, P = 0.018), blood cultures drawn (4 vs. 8 h, P < 0.001), antibiotic administration (5 vs. 8 h, P < 0.001), central venous pressure (8 vs. 11 h, P = 0.01), and SvcO2 monitoring (2.5 vs. 11 h, P = 0.222). The composition of the nursing team was the same around the clock; the medical team was reduced at night with a higher proportion of less differentiated doctors. The number of patients attending the Emergency Department was lower overnight. Hospital mortality rate was 34% in patients entering in the night period vs. 40% in those entering during the day (P = 0.281). CONCLUSION: Compliance with SSC recommendations was higher at night. A possible explanation might be the increased nurse to patient ratio in that period. Adjustment of the clinical team composition to the patients' demand is needed to increase compliance and improve prognosis.

Extralobar Pulmonary Sequestration.

Male, 71 year-old, asymptomatic, former smoker and previous history of lung tuberculosis. Referred to outpatient clinic due to left lower lobe consolidation diagnosed on non-contrasted CT scan, with increased uptake on PET-CT. Then, a contrast-enhanced CT scan revealed extralobar pulmonary sequestration with venous drainage to the left azygos vein (Blue arrow) and a double branch arterial supply from the thoracic aorta (Red arrow).

Does etiological investigation have an impact on the outcomes of community-acquired pneumonia? - A prospective cohort study.

INTRODUCTION: There is lack of evidence that etiological investigation influences outcomes in community-acquired pneumonia (CAP). Guidelines recommend diverse approaches to this matter. Our aim was to find if etiological investigation has an impact on CAP management and outcomes. METHODS: Prospective cohort study, conducted over a two years' period, in a community-based hospital, including all adult patients with CAP. Univariate and multivariate logistic regression modeling were performed to understand the association of etiological identification with CAP outcomes, particularly hospital mortality. RESULTS: A total of 660 cases of CAP were included, with a mean±sd age of 74±15 years and 58.9% of males. Etiology was documented in 33% of cases. Antibiotic (ATB) was modified in 148 patients, in 51 (34%) motivated by microbiological results. There was no significant impact on hospital mortality of microbiological documentation (35.5% vs 31.2%, p=0.352), or the fact that ATB was modified due to microbiological findings (27.0% vs 36.9%, p=0.272). When stratified by 3 subgroups of risk for drug-resistant pathogens (zero, one or two risk factors: being bed-ridden and/or ATB use within 90 days), etiology identification still did not influence mortality. When adjusted for CURB-65, Charlson's index, being bed-ridden, having had ATB or hospitalization within 90 days or coming from long-term care facilities, microbial identification was not associated with lower mortality. CONCLUSION: Etiological investigation of patients with CAP does not have an association with hospital mortality, irrespective of the risk for drug-resistant pathogens.

Predictors of early and long-term mortality after ICU discharge in critically ill COVID-19 patients: A prospective cohort study.

BACKGROUND: To mitigate mortality among critically ill COVID-19 patients, both during their Intensive Care Unit (ICU) stay and following ICU discharge, it is crucial to measure its frequency, identify predictors and to establish an appropriate post-ICU follow-up strategy. METHODS: In this multicentre, prospective cohort study, we included 586 critically ill COVID-19 patients. RESULTS: We observed an overall ICU mortality of 20.1% [95%CI: 17.1% to 23.6%] (118/586) and an overall hospital mortality of 25.4% [95%CI: 22.1% to 29.1%] (149/586). For ICU survivors, 30 days (early) post-ICU mortality was 5.3% [95%CI: 3.6% to 7.8%] (25/468) and one-year (late) post-ICU mortality was 7.9% [95%CI: 5.8% to 10.8%] (37/468). Pre-existing conditions/comorbidities were identified as the main independent predictors of mortality after ICU discharge: hypertension and heart failure were independent predictors of early mortality; and hypertension, chronic kidney disease, chronic obstructive pulmonary disease and cancer were independent predictors of late mortality. CONCLUSION: Early and late post-ICU mortality exhibited an initial surge (in the first 30 days post-ICU) followed by a subsequent decline over time. Close monitoring of critically ill COVID-19 post-ICU survivors, especially those with pre-existing conditions, is crucial to prevent adverse outcomes, reduce mortality and to establish an appropriate follow-up strategy.

Additional risk factors for infection by multidrug-resistant pathogens in healthcare-associated infection: a large cohort study.

BACKGROUND: There is a lack of consensus regarding the definition of risk factors for healthcare-associated infection (HCAI). The purpose of this study was to identify additional risk factors for HCAI, which are not included in the current definition of HCAI, associated with infection by multidrug-resistant (MDR) pathogens, in all hospitalized infected patients from the community. METHODS: This 1-year prospective cohort study included all patients with infection admitted to a large, tertiary care, university hospital. Risk factors not included in the HCAI definition, and independently associated with MDR pathogen infection, namely MDR Gram-negative (MDR-GN) and ESKAPE microorganisms (vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species, carbapenem-hydrolyzing Klebsiella pneumonia and MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), were identified by logistic regression among patients admitted from the community (either with community-acquired or HCAI). RESULTS: There were 1035 patients with infection, 718 from the community. Of these, 439 (61%) had microbiologic documentation; 123 were MDR (28%). Among MDR: 104 (85%) had MDR-GN and 41 (33%) had an ESKAPE infection. Independent risk factors associated with MDR and MDR-GN infection were: age (adjusted odds ratio (OR) = 1.7 and 1.5, p = 0.001 and p = 0.009, respectively), and hospitalization in the previous year (between 4 and 12 months previously) (adjusted OR = 2.0 and 1,7, p = 0.008 and p = 0.048, respectively). Infection by pathogens from the ESKAPE group was independently associated with previous antibiotic therapy (adjusted OR = 7.2, p < 0.001) and a Karnofsky index <70 (adjusted OR = 3.7, p = 0.003). Patients with infection by MDR, MDR-GN and pathogens from the ESKAPE group had significantly higher rates of inadequate antibiotic therapy than those without (46% vs 7%, 44% vs 10%, 61% vs 15%, respectively, p < 0.001). CONCLUSIONS: This study suggests that the inclusion of additional risk factors in the current definition of HCAI for MDR pathogen infection, namely age >60 years, Karnofsky index <70, hospitalization in the previous year, and previous antibiotic therapy, may be clinically beneficial for early diagnosis, which may decrease the rate of inadequate antibiotic therapy among these patients.

Risk factors for community-onset pneumonia caused by drug-resistant pathogens: A prospective cohort study.

INTRODUCTION: There is no consensual definition of risk factors for drug resistant pathogens (DRP) in community-onset pneumonia (COP). Healthcare-associated pneumonia criteria have been abandoned because they were found to have weak discriminative power. Our aim was to identify risk factors for DRP in COP. METHODS: Prospective cohort study, conducted over a two years' period, in a community-based hospital, including all adult patients with COP criteria. Univariate and multivariate logistic regression modeling were performed to understand the association of risk factors (demographic, clinical and epidemiological) with COP by a DRP (PES: Pseudomonas aeruginosa, extended-spectrum ß-lactamase producing Enterobacteriaceae, Methicillin-resistant Staphylococcus aureus; and other non-fermenting gram-negative bacteria, namely Acinetobacter baumannii). RESULTS: A total of 660 cases of COP were included, with a mean (±SD) age of 74±15 years and 58.9% of males. Microbiological documentation was possible in 32.6% of the cases. There were 197 cases selected for further analysis, of which 37 were cases of PES. The multivariate logistic regression model retained antibiotic use in the previous 90 days (adjusted OR=4.411, 95%CI [1.745-11.148]) and being bed-ridden (adjusted OR=5.492, 95%CI [2.121-14.222]), adjusted for Charlson's Index, CURB 65 and provenience from a long-term care facility. The area under the ROC curve for this model was 0.832, 95%CI [0.756-0.908], higher than the application of the HCAP criteria (AUROC = 0.676, 95%CI [0.582-0.770]). CONCLUSION: In this study, antibiotic use in the previous 90 days and being bed-ridden were independently associated with COP caused by DRP, after adjustment for Charlson's Index, CURB 65 and provenience from a long-term care facility.

Correlation of Estimated Creatinine Clearance and Glomerular Filtration Rate in Very Elderly Patients and Antibiotic Prescribing Errors: Cohort Study.

INTRODUCTION: Determination of renal function is particularly important when prescribing antibiotics to elderly patients. This study aims to determine the correlation between estimated creatinine clearance and the estimated glomerular filtration rate, for a hospitalized population of very elderly patients, and to audit antibiotic prescribing errors. MATERIAL AND METHODS: Retrospective cohort study of all patients ≥ 80 years hospitalized with antibiotic. Creatinine clearance was calculated using Cockcroft-Gault equation and estimated glomerular filtration rate by Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations. Dosing errors were determined through adjustment of daily define dose to renal function. RESULTS: The study included 589 patients. The correlation of Cockcroft-Gault with Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration was r = 0.98 and 0.96 for the minimum serum creatinine, and 0.97 and 0.93 for the maximum serum creatinine. Based on Cockcroft-Gault, there were errors in the daily defined dose in 45% in the minimum serum creatinine, and 52% in the maximum serum creatinine day. There was a discrepancy in the recording of errors of 14% to 16% when Cockcroft-Gault was compared with Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration. DISCUSSION: There was a good correlation of Cockcroft-Gault with the estimated glomerular filtration rate by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration. Regardless of the equation used to estimate renal function there was a high rate of antibiotic dosing errors documented in this population. CONCLUSION: This study supports the maintenance of the Cockcroft-Gault equation for drug dosing in the very elderly population. Further studies are needed to investigate underlying causes of prescribing errors.

Introdução: A determinação da função renal é particularmente importante na prescrição de antibióticos em doentes idosos. O objetivo deste estudo é correlacionar a clearance de creatinina com a taxa de filtração glomerular estimada, numa população hospitalizada de doentes muito idosos, e auditar os erros de prescrição antibiótica. Material e Métodos: Coorte retrospetivo de todos os doentes ≥ 80 anos hospitalizados com antibioterapia prescrita. A clearance de creatinina foi calculada através da equação Cockcroft-Gault, e a filtração glomerular estimada através das equações Modification of Diet in Renal Disease e Chronic Kidney Disease Epidemiology Collaboration. Os erros de prescrição foram determinados pelo ajuste da dose diária definida à função renal. Resultados: Foram incluídos 589 doentes. A correlação da Cockcroft-Gault com Modification of Diet in Renal Disease e Chronic Kidney Disease Epidemiology Collaboration foi r = 0,98 e 0,96 para a creatinina sérica mínima, e 0,97 e 0,93 para a creatinina sérica máxima. Com base na Cockcroft-Gault, a taxa de erro na dose diária definida foi 45% no dia da creatinina sérica mínima e 52% no dia da creatinina sérica máxima. Quando a Cockcroft-Gault foi comparada com a Modification of Diet in Renal Disease e a Chronic Kidney Disease Epidemiology Collaboration houve uma discrepância no registo de erros de 14% a 16%, respetivamente. Discussão: Verificou-se uma boa correlação entre a Cockcroft-Gault e as equações que calculam a filtração glomerular: Modification of Diet in Renal Disease ou Chronic Kidney Disease Epidemiology Collaboration. Independentemente da equação utilizada para estimar a função renal, foi documentada uma taxa elevada de erros na dose de antibióticos prescrita nesta população. Conclusão: Este estudo reforça a manutenção do uso da equação de Cockcroft-Gault para calcular a dose adequada de antibióticos na população muito idosa. Mais estudos são necessários para investigar as causas subjacentes aos erros de prescrição.

Haemodialysed patient with lung cancer in the COVID-19 era: a clinical challenge.

A 66-year-old man was referred to the oncological pneumology consultation due to a mass in the right upper lobe observed in a routine X-ray of the chest. The CT scan confirmed a mass in the same location. The biopsy revealed a lung adenocarcinoma. It was decided to start chemotherapy adapted to kidney function. In April 2020, the patient contracted SARS-CoV-2 infection and developed bilateral pneumonia with partial respiratory failure. He was transferred to the intensive care unit, where he had a positive evolution. In the next 5 months, there was a clinical improvement; however, the CT scan of the chest showed disease progression. After a new multidisciplinary approach, it was decided to start a second line with atezolizumab. After four cycles of atezolizumab, there was a clear clinical improvement, and a reduction by more than 50% in the tumour size, without significant adverse effects.

Nursing Epidemiological Approach of Hypertension Management in a Public Health Service from the Northern Region of Portugal.

BACKGROUND: Epidemiological surveillance of a nursing diagnosis is an approach anchored in a post-modern epidemiology focused on a person's health disease responses. Regarding public health priorities, the population where our study occurred had as a priority problem arterial hypertension. Related to this chronic disease, nursing diagnoses about health disease responses in primary healthcare has, as a major focus, Therapeutic Regimen Management. Our aim was to study the nursing diagnosis in this issue from an epidemiological approach. METHODS: A descriptive study from an epidemiological approach was developed, analyzing nursing diagnoses in hypertensive patients. RESULTS: We found 17.7% of undiagnosed patients and better diagnoses in patients with complications than in those without complications. CONCLUSIONS: Nursing records need to be improved in order to promote more robust studies in the post-modern epidemiology for the future.

Reducing mortality in severe sepsis with the implementation of a core 6-hour bundle: results from the Portuguese community-acquired sepsis study (SACiUCI study).

INTRODUCTION: To evaluate the impact of compliance with a core version of the Surviving Sepsis Campaign 6-hour bundle on 28 days mortality. METHODS: Cohort, multi-centre, prospective study on community-acquired sepsis (CAS). RESULTS: Seventeen intensive care units (ICU) entered the study. Over a one year period, 4,142 patients were enrolled in the study. Of the 897 (24%) admitted with CAS, 778 (87%) had severe sepsis or septic shock on ICU admission. In the first six hours of hospital admission: (1) 62% had serum lactate measured; (2) 69% fluids administered; (3) 77% specimens collected for microbiology before antibiotic administration; (4) 48% blood cultures obtained; (5) 52% antibiotics administered within the first hour of the diagnosis; (6) vasopressors were given in 78%; (7) 56% had central venous measurement (CVP) measurement; (8) 17% had a central venous oxygen saturation (ScvO2) measurement; (9) dobutamine was administered in 52%. Compliance with all actions 1 to 6 (core bundle) was associated with an odds ratio (OR) of 0.44 [95% confidence interval (CI) = 0.24-0.80] in severe sepsis and 0.49 (95% CI = 0.25-0.95) in septic shock, for 28 days mortality. This corresponded to a number needed to treat of 6 patients to save one life. CONCLUSIONS: Compliance with this core bundle was associated with a significant reduction in the 28 days mortality. Urgent action should be taken in order to ensure that early sepsis diagnosis is followed by full completion of this "core bundle" followed by activation of expertise help in severe sepsis.