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Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopment disorders in the world. Clinical guidelines for ADHD recommend multimodal treatment approaches, with current evidence suggesting that medication, including methylphenidate and various amphetamine formulations, in conjunction with psychosocial treatment are most effective in the short-term and long term. Over the last decade, an increasing number of studies investigating non-pharmacological treatments have been published, such as cognitive therapy, Neurofeedback (NF), Transcranial direct current stimulation with the aim of treating ADHD patients. Objectives We comprehensively reviewed literature searching for studies on the effectiveness and specificity of NF for the treatment of ADHD. The aim of this review is to understand if there is scientific evidence in using of electroencephalogram (EEG)-Neurofeedback for treating patients with ADHD. Methods We did a non systemathic review using pubmed and google schoolar databases in order to analyze the influence and effects of therapy in patients diagnosed with ADHD and under treatment based on EEG Neurofeedback. We analyzed 18 systhematic reviews and metha-analysis and 2 case control studies. Results Accourding to the systhematic reviews results showed positive and significant effects in the visual memory, attention and visual recognition (spatial working memory). EEG also showed improvement in upper alpha activity in a resting state (open-eyed) measured from the occipital area, which similarly indicated improvement in the cognitive domain (attention). Compared to non-active control treatments, NF appears to have more durable treatment effects, for at least 6 months following treatment. Conclusions In conclusion, it is possible to affirm that a neuromodulating effect of the therapy positively influences cognitive processes, mood, and anxiety levels in patients with ADHD and is associated with significant long-term reduction in symptoms. Though limitations exist regarding conclusions about the specific effects of NF, the review documents improvements in school, social, and family environments. However, future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer and more studies are needed for a properly powered comparison of follow-up effects between NF and active treatments and to further control for non-specific effects. Disclosure of Interest None Declared

Introduction Home hospitalization is an alternative to conventional hospitalization in several areas of medicine. In Portugal, we are now starting to think about its implementation in Psychiatry, given the positive experience of its use in other countries. Objectives Understand the advantages and disadvantages of a home hospitalization model and its logistical and clinical framework in an integrated community-focused care model. Methods We performed a literature review using Pubmed databases and UpToDate on home hospitalization, inpatient care and community-focused care model Results We have found reports of centers with experience in home hospitalization in Psychiatry, but there is still a notable lack of studies in this area. There is a discrepancy between the care needs of patients and the existence of community services for the treatment of mental illness. Home hospitalization is considered when there is partial remission of the symptomatology that motivated the hospitalization. Albeit demanding inclusion criteria limit eligible patients, there are several advantages with this hospitalization model: 1) it favors agility in the transition from hospital to home, with direct observation of contextual factors that may influence psychiatric decompensation, 2) integrates the patient in his natural environment, promoting his autonomy,; 3) allows psychoeducation of the family; 3) guarantees the continuity of the therapeutic process initiated in the hospital, 4) optimizes resources and cost-effectiveness, 5) prevents relapses and the “revolving-door “phenomenon. Conclusions We have found that a model of home hospitalization is a valuable element that should be included in an integrated system of psychiatric care. Disclosure No significant relationships.

The calcium ion (Ca2+) plays a fundamental role in the metabolism and cell physiology of eukaryotic cells. In general, increases in cytosolic Ca2+ may come from both of the extracellular environment through specific channels and/or calcium release from intracellular stores. The mechanism by which the ion calcium (Ca2+) is released from intracellular stores in higher eukaryotes is well known; however, in lower eukaryotes is still a subject of study. In the present work, it was elucidated that Trypanosoma cruzi epimastigotes can release Ca2+ from intracellular stores in response to high osmolarity, in a process involving a protein kinase-regulated Na+/H+ exchanger present in the acidocalsisomes of the parasite. In addition, we demonstrated that epimastigote membranes are able to release Ca2+ in response to exogenous activators of both inositol 1,4,5-triphosphate (IP3) and Ryanodine receptors. Furthermore, we also summarize the involvement of calcium-related signaling pathways in biochemical and morphological changes triggered by hyperosmotic stress in T. cruzi epimastigotes.

Objective: To describe the successful implementation of an enhanced public health surveillance system based on early detection, tracing contacts, and patient follow-up and support. Study design: A prospective observational cohort study conducted in Serrana, São Paulo State, Brazil. Methods: The implementation was based on four axes: increasing the access to SARS-CoV-2 testing; correct swab collection; testing patients with mild symptoms; and patient follow-up. Positivity rate, patient demographic and clinical characteristics, dynamics of disease severity, SARS-CoV-2 genome evolution, and the impact on COVID-19 research were assessed from August 23, 2020 to February 6, 2021 (between epidemiological week 35/2020 and 5/2021, a total of 24 weeks). Results: The number of sites collecting rt-PCR for SARS-CoV-2 was increased from one to seven points and staff was trained in the correct use of personal protective equipment and in the swab collection technique. During the study period, 6728 samples were collected from 6155 participants vs. 2770 collections in a similar period before. SARS-CoV-2 RNA was detected in 1758 (26.1%) swabs vs. 1117 (36.7%) before the implementation of the surveillance system (p

Introduction: improper use of medication is becoming more frequent and can cause physical or physiological damage. Objective: to determine the frequency of potentially inappropriate prescriptions of cardiovascular drugs according to Beers’ criteria in a population of colombian patients. Method: cross-sectional study conducted during november 2016 using a population database of 326,192 adults over 65 years of age who were eligible to receive drugs included in the cardiovascular system category according to the Beers’ criteria. The frequency of potentially inappropriate prescriptions was determined and investigated in relation to sociodemographic variables. Results: the mean subject age was 74.6±7.6 years (range:65-100 years). It was found that 11.3% (n=36894) of the elderly presented at least one potentially inappropriate prescription for cardiovascular conditions. The most frequent finding was the use of aspirin in patients older than 80 years of age followed by the use of prazosin for hypertension in patients over 65 years of age or in patients who consulted emergency services for syncope. The other criteria were present in less than 1% of patients, and in 16 out of 33 treatment drugs, no patients exposed to potentially inappropriate prescriptions were found. Within the criteria based on drug-drug interactions, the most frequent were loop diuretics along with prazosin (6.4%). Conclusions: the prevalence of potentially inappropriate prescriptions in an elderly population of patients in Colombia is lower than that reported worldwide. In addition, there is a need to re-evaluate the Beers’ criteria in this population and adjust the guidelines according to results of pharmacovigilance of active pharmaceutical substances available in Colombia. Resumen: Introducción: el uso incorrecto de medicamentos es cada vez más frecuente y puede causar daños físicos o fisiológicos. Objetivo: determinar la frecuencia de las prescripciones de medicamentos de uso cardiovascular potencialmente inapropiadas según criterios de Beers en una población de pacientes colombianos. Métodos: estudio de corte transversal, a partir de una base de datos de una población de 326.192 adultos mayores de 65 años, durante el mes de noviembre de 2016, susceptibles de recibir medicamentos incluidos en los criterios de Beers en la categoría de sistema cardiovascular, determinando la frecuencia de prescripciones potencialmente inapropiadas, así como la identificación de variables sociodemográficas. Resultados: la edad promedio fue de 74,6±7,6 años (rango 65-100 años). Se halló que el 11,3% (n=36894) de los ancianos tuvo al menos una prescripción potencialmente inapropiada para condiciones cardiovasculares. El criterio más frecuente fue el uso de aspirina en mayores de 80 años, seguido del empleo de prazosín para la hipertensión arterial en mayores de 65 años, o en pacientes que consultaron por síncope a los servicios de urgencias. Los demás criterios se presentaban en menos del 1% de pacientes y en 16 de 33 fármacos de cuidado no se halló ningún paciente expuesto. Entre los criterios basados en interacciones fármaco-fármaco, el más frecuente fue diuréticos de asa junto con prazosín (6,4%). Conclusiones: la prevalencia de prescripciones potencialmente inapropiadas en una población de ancianos colombianos es menor a la reportada en el mundo. Además, se plantea la necesidad de reevaluar los criterios de Beers en dicha población y ajustarlos de acuerdo con los informes de farmacovigilancia y principios activos disponibles en Colombia.

Chronic kidney disease (CKD) is a significant public health challenge with a substantial associated risk of mortality, morbidity, and health care expenditure. Culprits that lead to development and progression of CKD are multifaceted and heterogenous in nature. This notion underscores the need for diversification of animal models to investigate its pathophysiology, related complications, and to subsequently enable discovery of novel therapeutics. Importantly, animal models that could recapitulate complications of CKD in both genders are desperately needed. Cardiovascular disease is the most common cause of death in CKD patients that may be due in part to high prevalence of vascular calcification (VC). Using DBA/2 mice that are susceptible to development of VC, we sought to investigate the feasibility and reproducibility of a unilateral ischemia-reperfusion model followed by contralateral nephrectomy (UIRI/Nx) to induce CKD and its related complications in female and male mice. Our results demonstrate that irrespective of gender, mice faithfully displayed complications of moderate CKD following UIRI/Nx as evidenced by significant rise in serum creatinine, albuminuria, higher degree of collagen deposition, elevated expression of classic fibrotic markers, higher circulating levels of FGF-23, PTH and hepcidin. Moreover, we corroborate the osteoblastic transition of aortic smooth muscle cells and cardiomyocytes based on higher levels of osteoblastic markers namely, Cbfa-1, osteopontin, osteocalcin, and osterix. Our data confirms a viable, and consistent model of moderate CKD and its associated complications in both male and female mice. Furthermore, early evidence of osteoblastic transition of cardiovascular system in this model confirms its suitability for studying and implementing potential preventive and/or therapeutic approaches that are urgently needed in this field.

Introduction. Lipid-lowering drugs, especially statins, have shown great relevance in preventing and treating cardiovascular diseases. Objective. To determine the prescription patterns of lipid-lowering drugs and the variables associated with their use in a Colombian population. Materials and methods. This is a cross-sectional descriptive study. From a drug dispensing database of approximately 4.5 million Colombian health system affiliates, patients of all ages and both sexes treated with lipid-lowering agents (statins, fibrates, ezetimibe) were identified between January and March, 2017. Demographic, pharmacological and co-medication variables were included. Results. In total, 103,624 patients were identified as being treated with lipid-lowering agents. The average age was 67.5 years, and 49.8% were 65 years or older. Women comprised 58.0% of the patients. Statins were the most used (n=96,910; 93.5%), and atorvastatin (n=80,812; 78.0%) and lovastatin (n=12,621; 12.2%) were the most frequent. The mean atorvastatin dose was 30.3 mg/day, and 49.9% of its users received presentations of 40 mg or more. A total of 9,258 (8.9%) patients received fibrates, and only 780 (0.8%) were taking ezetimibe. Of this population, 94.9% were treated with lipid-lowering monotherapy, and 97.3% (n=100,813) had co-medication for their comorbidities, with the most frequent being antihypertensive (89.1%), antiplatelet (57.8%), antidiabetic (31.5%) and antiulcerative agents (34.2%). Conclusions. Atorvastatin is currently the most frequently used lipid-lowering drug in this group of Colombian patients, especially in monotherapy and at doses close to the defined daily dose. Only half received high-intensity doses. New studies are required to verify the efficacy of these therapies.

Introduction: The impact of COVID-19 pandemics on cardiovascular diseases (CVD) may be caused by health system reorganization and/or collapse, or from changes in the behaviour of individuals. In Brazil, municipalities were empowered to define regulatory measures, potentially resulting in diverse effects on CVD morbimortality. Objective: To analyse the impact of COVID-19 pandemics on CVD outcomes in Belo Horizonte (BH), the sixth greater capital city in Brazil, including: mortality, mortality at home, hospitalizations, intensive care unit utilization, and in-hospital mortality; and the differential effect according to sex, age range, social vulnerability, and pandemic’s phase. Methods: Ecological study analysing data from the Mortality and Hospital Information System of BH residents aged ≥30 years. CVD was defined as in Chapter IX from ICD-10. Social vulnerability was classified by a composite socioeconomic index as high, medium and low. The observed age-standardized rates for epidemiological weeks 10–48, 2020, were compared to the expected rates (mean of 2015–2019). Risk ratios (RiR) were analysed and 95% confidence intervals were calculated for all estimates. Population projected to 2020 for BH and its census tracts were used to calculate rates. Results: We found no changes in CVD mortality rates (RiR 1.01, 95%CI 0.96–1.06). However, CVD deaths occurred more at homes (RiR 1.32, 95%CI 1.20–1.46) than in hospitals (RiR 0.89, 95%CI 0.79–0.99), as a result of a substantial decline in hospitalization rates, even though proportional in-hospital deaths increased. The rise in home deaths was greater in older adults and in had an increasing gradient in those more socially vulnerable (RiR 1.45); for high (RiR 1.45), medium (RiR 1.32) and low vulnerability (RiR 1.21). Conclusion: The greater occurrence of CVD deaths at home, in parallel with lower hospitalization rates, suggests that CVD care was disrupted during the COVID-19 pandemics, which more adversely affected older and more socially vulnerable individuals, exacerbating health inequities in BH.

Background Type 2 diabetes mellitus (T2DM) greatly increases cardiovascular risk. Primary and secondary cardiovascular prevention lead to lower cardiovascular events, improved quality of life and lower costs related to complications. Objective To estimate the proportion of patients with T2DM undergoing drug therapy for cardiovascular prevention (aspirin and statins) in Colombia and to describe the change in patterns of use between 2008 and 2018. Methods This was a cross-sectional study comparing prescriptions for aspirin and statins in 2008 and in 2018 in outpatients diagnosed with T2DM. Records were obtained from a national drug claim database. The proportion of use of cardiovascular prevention drugs and antidiabetic drugs, medications for comorbidities and sociodemographic variables were analyzed for both periods. Results In total, 26 742 patients in 2008 and 188 321 in 2018 with a diagnosis of T2DM treated with antidiabetic drugs were identified, among whom 57.5% and 44.2% received aspirin and 44.9% and 60.2% received statins, respectively. The use of high-intensity statins increased from 1.1% in 2008 to 95.2% in 2018. The probabilities of receiving drugs in 2008 and in 2018 were higher for men (OR: 1.12, 95% CI: 1.06-1.17 and OR: 1.26, 95% CI: 1.23-1.28, respectively), for those persons over 75 years of age (OR: 6.5, 95% CI: 5.3-7.9 and OR: 5.8, 95% CI: 5.4-6.2) and for those who also received clopidogrel (OR: 5.8, 95% CI: 4.4-7.6 and OR: 2.2, 95% CI: 2.1-2.4). Conclusions The use of high-intensity statins in patients with T2DM has increased significantly in the last decade, which should reduce cardiovascular events, morbidity and mortality.

Background Ischemic heart disease is the leading cause of death in the world and is associated with dyslipidemia, high blood pressure, diabetes mellitus, and other factors. Objective To determine the clinical effectiveness on the lipid profile of the rosuvastatin + fenofibric acid combination in Colombian patients with high cardiovascular risk and mixed dyslipidemia. Methods Longitudinal observational study in a random sample of patients with a diagnosis of mixed dyslipidemia and moderate, high, or very high cardiovascular risk who were treated with rosuvastatin + fenofibric acid. Anthropometric, clinical, laboratory, comorbidity, and pharmacological variables were identified. Effectiveness on the lipid profile was determined. Results A total of 386 patients were analyzed. They had a mean age of 60.8 ± 11.4 years, 53.1% were female, and 75.6% had high/very high cardiovascular risk. The initial evaluation showed a mean LDL cholesterol of 138.4 ± 67.1 mg/dL and triglycerides of 679.7 ± 573.6 mg/dL. At the end of follow-up, mean LDL cholesterol was 87.5 ± 41.2 mg/dL (reduced by 43.3%; P

Background: The appearance of inhibitory antibodies against antihemophilic factors is one of the most serious complications related to hemophilia. Objective: The objective of this study was to identify variables and factors related to the development of inhibitory antibodies in a group of patients undergoing antihemophilic therapy in Colombia. Methods: A case-control study in patients with hemophilia treated in Specialized Healthcare Provider Institutions (IPS-E) in 21 cities of Colombia of any age and with a diagnosis of inhibitory antibodies against factor VIII or IX during 2016. Four controls per case paired by age and type of hemophilia were used. Sociodemographic, clinical, and pharmacological variables were identified and analyzed. Results: Seventeen patients with inhibitory antibodies and 68 controls with hemophilia were identified. The mean age was 28.3 ± 17.8 years. A total of 94.1% had hemophilia A, and 88.2% of the cases and 50.0% of the controls had severe hemophilia; 47.1% of the cases and 54.4% of the controls were receiving prophylaxis with coagulation factors. Multivariate analysis showed that having severe hemophilia (OR:17.0, 95%CI:1.32–219.60) and lack of knowledge of the coagulation factor with which the patient was treated before entering the care program in the IPS-E (OR:8.9, 95%CI:1.82–43.75) were significantly associated with a higher probability of developing inhibitory antibodies. Conclusion and relevance: Coagulation factors associated with the development of inhibitory antibodies were severe hemophilia and lack of knowledge of the type of factor used prior to entering the follow-up cohort.

Background. Neuropathic pain has a prevalence of 2–17% in the general population. Diagnosis and treatment of neuropathic pain are not fully described in different populations. The aim was to determine the treatment patterns and direct costs of care associated with the management of neuropathic pain from the onset of the first symptom to up to two years after diagnosis. Methods. From a drug-claim database, a cohort of randomly selected outpatients diagnosed with neuropathic pain was obtained from an insurer in Colombia and followed up for two years after diagnosis. The clinical records were reviewed individually to identify the study variables, including the time needed to make the diagnosis, the medical and paraclinical resources used, the pharmacological therapy for pain management, and the direct costs associated with care. Results. We identified 624 patients in 49 cities, with a mean age of 50.3 ± 14.1 years, of which 324 were men (51.9%). An average of 90 days passed from the initial consultation until the diagnosis of neuropathic pain, the most frequent being lumbosacral radiculopathy (57.9%). 34.5% of the cohort had at least one diagnostic imaging procedure, and 16% had an electromyography. On average, they were treated by a general practitioner twice. 91.7% received initial treatment with tramadol, carbamazepine, amitriptyline, imipramine, or pregabalin, and 60.4% received combined therapy. The mean cost of care for two years for each patient was US$246.3. Conclusions. Patients with neuropathic pain in Colombia are being diagnosed late, are using therapeutic agents not recommended as first-line treatment by clinical practice guidelines, and are being treated for short periods of time.

The objective was to determine the trend in the use of opioid analgesics in a cohort of patients diagnosed with and treated for rheumatoid arthritis (RA) in 24 cities in Colombia. This retrospective cohort study included adult patients diagnosed with RA, which was managed in a specialized institution in Colombia between January 2011 and December 2012. The first rheumatology visit was recorded as an index date, and monthly monitoring of the analgesic medication received was performed until December 2017. Sociodemographic variables, the use of opioids, and concomitant prescriptions were evaluated. A total of 1,329 patients diagnosed with and treated for RA were included; they had a mean age of 61.2 ± 11.8 years and were predominantly females (n = 936; 82.9%). A total of 1,129 (84.9%) subjects used opioids for at least one month, and a growing trend, from 13.5% to 21.4%, was observed in patients who received opioids every month throughout a 7-year follow-up of the cohort. In total, 46.7% of the cases used opioids for more than 12 months. The most commonly used opioids were codeine (76.3%) and tramadol (71.1%). All patients received conventional disease-modifying antirheumatic drugs (DMARDs), 85.6% received systemic corticosteroids, 73.9% received nonsteroidal anti-inflammatory drugs, and 15.9% received biological DMARDs. A high proportion of opioid use was shown for pain management in patients with RA, in many cases for more than 12 months, in whom the efficacy and especially safety, related to the risk of dependence, should be monitored.

To advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions, and we find a broad concordance between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. Our results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation in Drosophila.

Antimicrobials are frequently inappropriately prescribed for the management of upper respiratory tract infections (URTIs); therefore, the frequency of antibiotic prescriptions for patients with viral URTIs was assessed in this study. A cross-sectional study, including ambulatory patients diagnosed with viral URTI, was conducted, and records of antimicrobial prescriptions were obtained. Sociodemographic, clinical (diagnostic), and pharmacological (antimicrobial) variables were assessed. Through multivariate analysis, variables associated with the use of antibiotics for viral infections were identified. A total of 341,182 patients with viral URTIs were identified. The patients, who were from 26 different departments of Colombia, had a mean age of 29.7 ± 23.5 years and a female predominance of 58.7% (n = 200,195). The most frequent viral infections were as follows: acute rhinopharyngitis (common cold) (n = 206,211; 60.4%); unspecified acute tonsillitis (n = 27,432; 8.0%); and acute pharyngitis (n = 26,411; 7.7%). A total of 24.8% of the patients (n = 84,453) received a prescription for antibiotics, predominantly penicillins (n = 61,871; 18.1%) and cephalosporins (n = 10,926; 3.2%). Patients treated in Atlántico, Valle, and Risaralda departments, along with those older than 5 years, were more likely to receive antibiotics for the treatment of viral infections. Antibiotics are frequently prescribed for the management of URTIs, which is considered an inappropriate practice due to a lack of clinical benefits, increased generation of antimicrobial resistance, and a risk of adverse reactions due to the use of medications that patients do not require. Drug utilization studies are a great tool for monitoring how antibiotics are being used and planning interventions to improve their use.

Introduction: Since the beginning of the epidemic, human immunodeficiency virus (HIV) has taken more than 36 million lives. Objective: To determine the antiretroviral drug prescription patterns in a population of individuals with HIV infection in Colombia. Materials and methods: Cross-sectional study analyzing the profiles of patients treated with antiretroviral drugs between April 1st and September 30th, 2015. The sociodemographic, pharmacological, and comorbidity variables were identified. Individuals with a positive diagnosis of HIV of all ages and both genders were included. Results: We found 641 patients with a mean age of 39.0±17 years who were predominantly male (60.2%). The most used medications were lamivudine-zidovudine (51.6%), lopinavir-ritonavir (36%) and efavirenz (24.5%). The combination of lamivudine-zidovudine plus lopinavir-ritonavir was the most prescribed regimen (29.5%), but a total of 80 different regimens was identified. Being an adult between the ages of 45-64 years (OR=2.25; 95%CI 1.367-3.713) was associated with a greater probability of receiving 4 or more antiretrovirals. A total of 267 (41.6%) patients used at least one comedication (range: 1-18 drugs), especially anti-ulcer (57.3%), lipid-lowering (28.8%) and anti-hypertensive (28.5%) drugs. Conclusions: Patients undergoing antiretroviral treatment are receiving medications with elevated intrinsic values at the recommended doses and present comorbidities associated with chronic agerelated conditions. However, these patients receive a great variety of regimens that are not included in the clinical practice guidelines.

Objective: The objective was to determine the effectiveness of two piperacillin–tazobactam molecules in terms of all-cause mortality, mortality by infection, and hospital stay. Methods: A cohort study was performed involving patients treated with piperacillin–tazobactam at a clinic in Colombia. The patients were divided into those who received the innovator piperacillin–tazobactam (from July to December 2014) and those who received the generic piperacillin–tazobactam (from January to June 2015). Socio-demographic, clinical (all-cause mortality, death by infection, days of hospitalization), microbiological, pharmacological, and comorbidity variables were evaluated. Multivariate analyses were performed. Results: A total of 279 patients were included: 140 treated with the innovator piperacillin–tazobactam and 139 with the generic piperacillin–tazobactam. The median age was 63 years, and 56% of the patients were male. There was no statistically significant difference in death from all causes (22.9% vs. 14.4%, p = 0.069), death by infection (7.9 vs. 10.8%, p = 0.399), or hospital stay (18.1 ± 16.2 vs. 15.7 ± 11.6 days, p = 0.178) between the innovator and generic piperacillin–tazobactam, respectively. Conclusions: The generic piperacillin–tazobactam was equivalent to the innovator piperacillin–tazobactam with regards to all-cause mortality, mortality by infection, hospital stay, and safety, and at a lower cost, which may be useful for decision-makers in hospitals. Keywords: Critical care, Treatment outcome, Piperacillin