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Background: Computerized Provider Order Entry (CPOE) and Clinical Decision Support System (CDSS) help practitioners to choose evidence-based decisions, regarding patients’ needs. Despite its use in developed countries, in Brazil, the impact of a CPOE/CDSS to improve cefazolin use in surgical prophylaxis was not assessed yet. Objective: We aimed to evaluate the impact of a CDSS to improve the use of prophylactic cefazolin and to assess the cost savings associated to inappropriate prescribing. Methods: This is a cross-sectional study that compared two different scenarios: one prior CPOE/CDSS versus after software implementation. We conducted twelve years of data analysis (3 years prior and 9 years after CDSS implementation), where main outcomes from this study included: cefazolin Defined Daily Doses/100 bed-days (DDD), crude costs and product of costs-DDD (cost-DDD/100 bed-days). We applied a Spearman rho non-parametric test to assess the reduction of cefazolin consumption through the years. Results: In twelve years, 84,383 vials of cefazolin were dispensed and represented 38.89 DDD/100 bed-days or USD 44,722.99. Surgical wards were the largest drug prescribers and comprised >95% of our studied sample. While in 2002, there were 6.31 DDD/100 bed-days, 9 years later there was a reduction to 2.15 (p

Objective: To assess the role of social risk factors on adherence to tyrosine kinase inhibitors (TKI) therapy in chronic myeloid leukemia (CML) patients. Methods: This is a retrospective study and eligible patients were adults with CML on TKI treatment. Cases of no adherence to treatment were confirmed during pharmacists’ consultation (patient-reported adherence). Baseline characteristics between groups were compared between cases and controls groups. Risk factors identified in bivariate analysis (p

Information about the morphology of the intracranial pressure waveform, as well as the variations in intracranial pressure (ICP) and compliance in pediatric patients are essential to diagnose and predict the progression of various neurological conditions. However, there is no information on the morphology of the IP waveform in neurologically healthy pediatric patients. In the present study, intracranial compliance was therefore analyzed in neurologically healthy patients with the aid of a noninvasive device. The study was an observational, cross-sectional study. Fifty-five neurologically healthy participants were included. Data on intracranial compliance with the patient in two positions, lying down (0°) and seated (45°), were collected with a noninvasive extracranial sensor, which allowed the intracranial pressure waveforms to be recorded. The values of the ratio P2/P1 were then analyzed. A questionnaire (with a scale from zero to ten, where ten corresponds to the highest level of satisfaction) was applied for patients to evaluate their satisfaction with the sensor. Patients were 10 years old (average), and most of them were (58%). Mean P2/P1 ratio was 0.94 (sd = 0.14) in the supine position and 0.91 (sd = 0.15) in the seated position. Participants were satisfied with the length of time for which the equipment was used (9.8, sd = 0.71). The device did not cause any discomfort. The noninvasive method used was well accepted by the patients. Intracranial compliance values were determined by analysis of the P2/P1 ratio in neurologically healthy pediatric population.Trial registration: Brazilian Registry of Clinical Trials Identifier: RBR-5j74ddg., (© 2024. The Author(s).)

Background: The purpose of this study was to review and summarize the association between preoperative magnetic resonance imaging (MRI) and surgical outcomes in women with newly diagnosed invasive breast cancer from published randomized controlled trials (RCT)., Materials and Methods: Two independent researchers conducted a systematic review through a comprehensive search of electronic databases, including PubMed, Medline, Embase, Ovid, Cochrane Library, and Web of Science. If there was disagreement between the two reviewers, a third reviewer assessed the manuscript to determine whether it should be included for data extraction. The quality of the papers was assessed using the risk of bias tool, and the evidence was analyzed using GRADE. Meta-analyses using a fixed-effects model were used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI)., Results: Initially, 21 studies were identified, 15 of which were observational comparative studies. A total of five RCTs were included, and they suggested that preoperative MRI significantly reduced the rate of immediate breast-conserving surgery and increased the risk for mastectomy., Conclusions: From the RCT perspective, preoperative MRI for newly diagnosed invasive breast cancer did not improve surgical outcomes and may increase the risk of mastectomy., (© 2024. The Author(s).)

Pathological complete response (pCR) is an important surrogate outcome to assess the effects of neoadjuvant chemotherapy (NAC). Nomograms to predict pCR have been developed with local data to better select patients who are likely to benefit from NAC; however, they were never critically reviewed regarding their internal and external validity. The purpose of this systematic review was to critically appraise nomograms published in the last 20 years (2010-2022). Articles about nomograms were searched in databases, such as PubMed/MEDLINE, Embase and Cochrane. A total of 1120 hits were found, and seven studies were included for analyses. No meta-analysis could be performed due to heterogeneous reports on outcomes, including the definition of pCR and subtypes. Most nomograms were developed in Asian centers, and nonrandomized retrospective cohorts were the most common sources of data. The most common subtype included in the studies was triple negative (50%). There were articles that included HER2+ (>80%). In one study, scholars performed additional validation of the nomogram using DFS and OS as outcomes; however, there was a lack of clarity on how such endpoints were measured. Nomograms to predict pCR cannot be extrapolated to other settings due to local preferences/availability of NAC. The main gaps identified in this review are also opportunities for future nomogram research and development.

Introduction: The therapeutic plasma exchange (TPE) controls the systemic cytokine level and might improve the immune response in patients with severe Coronavirus (COVID-19) infection. To date, in developing countries, no study has explored the effectiveness and risk factors in a population with severe COVID-19 exposed to the TPE., Method: We described the risk factors associated with survival rates higher than 28 days and length of stay (LOS) in the intensive care unit (ICU) shorter than 15 days. Severe COVID-19 cases treated with TPE were included, from August 2020 to June 2021. Survival analysis with Kaplan-Meier curves, log-rank tests and multivariate logistic regressions were conducted to assess patient-related factors that could predict a higher survival rate and the ICU LOS., Results: A total of 99 patients with severe COVID-19 who had received TPE were followed during their hospital stay and for 28 days after discharge. The sample was composed of men (63%) aged 56 ± 16 years. The overall survival rate at 28 days was 80%. The ICU LOS (p = 0.0165) and mechanical ventilation (MV) (p = 0.00008) were considered factors that could increase the risk of death. Patient-related factors that influenced the 28-day mortality were the smoking status (OR = 5.8; 95%CI 1.5, 22) and history of oncologic or non-malignant hematologic diseases (OR = 5.9; 95%CI 1.2, 29)., Conclusion: Patients with severe COVID-19 exposed to the TPE were associated with a 20% risk of death in a 28-day observation window, appearing to be lower than previous treatments. Active smoking, cancer and immunosuppressive conditions should be considered as relevant variables to be controlled in future trials on the TPE and COVID-19., Competing Interests: Conflicts of interest None., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Background: Randomized controlled trials (RCTs) and observational studies have compared the efficacy and safety of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis., Objectives: Compare TAVR and SAVR in patients with different surgical risks, population characteristics, and different transcatheter prosthetic valves., Methods: An overview of systematic reviews (SRs) was conducted following a structured protocol. Results were grouped by surgical risk, population characteristics, and different valves. RCTs in the SRs were reanalyzed through meta-analyses, and the results were summarized using the GRADE method. The adopted level of statistical significance was 5%., Results: Compared to SAVR, patients with high surgical risk using TAVR had a lower risk of (odds ratio, 95% confidence interval, absolute risk difference) atrial fibrillation (AF) (0.5, 0.29-0.86, -106/1000) and life-threatening bleeding (0.29, 0.2-0.42, -215/1000). Patients with intermediate surgical risk had a lower risk of AF (0.27, 0.23-0.33, -255/1000), life-threatening bleeding (0.15, 0.12-0.19, -330/1000), and acute renal failure (ARF) (0.4, 0.26-0.62, -21/1000). Patients with low surgical risk had a lower risk of death (0.58, 0.34-0.97, -16/1000), stroke (0.51, 0.28-0.94, -15/1000), AF (0.16, 0.12-0.2, -295/1000), life-threatening bleeding (0.17, 0.05-0.55, -76/1000), and ARF (0.27, 0.13-0.55, -21/1000), and had a higher risk of permanent pacemaker implantation (PPI) (4.22, 1.27-14.02, 141/1000). Newer generation devices had a lower risk of AF than older generations, and patients using balloon-expandable devices did not experience higher risks of PPI., Conclusions: This paper provides evidence that patients at low, intermediate, and high surgical risks have better outcomes when treated with TAVR compared with SAVR.

During the COVID-19 pandemic, several screening exams were postponed, including mammograms. The aim of this study was to evaluate the impact of COVID-19 in mammographic screening in Brazil, considering 2015 to 2021. This was descriptive ecologic study based on the retrospective data of Brazil's mammographic screening program. A Brazilian national screening database (DATASUS - SISCAN (Cancer System Information)) was used as the data source, and the data in this database are publicly available for download and analysis. We report the number of screening rate from January 2015 to December 2021, using 2020 as reference year for COVID-19. From 2015 to 2021, 10,763,894 mammograms were performed and included in the analysis. Reductions of 39.6% and 13.3% were found in 2020 in 2021, respectively. During the pandemic's peak, the reduction was more pronounced, with maximum reductions of 82.4% in May 2020 and 34.8% in April 2021. There was an increase in the number of mammograms performed on high-risk patients from 11.2% in 2020 to 13.9% in 2021. This research demonstrated a decline in the breast cancer screening rate during the two years of the COVID-19 pandemic; this reduction will increase the burden of advanced breast cancer, potentially impacting morbidity and mortality related to this neoplasm., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Healthcare decision-makers face difficult decisions regarding COVID-19 booster selection given limited budgets and the need to maximize healthcare gain. A constrained optimization (CO) model was developed to identify booster allocation strategies that minimize bed-days by varying the proportion of the eligible population receiving different boosters, stratified by age, and given limited healthcare expenditure. Three booster options were included: B 1 , costing US $1 per dose, B 2 , costing US $2, and no booster (NB), costing US $0. B 1 and B 2 were assumed to be 55%/75% effective against mild/moderate COVID-19, respectively, and 90% effective against severe/critical COVID-19. Healthcare expenditure was limited to US$2.10 per person; the minimum expected expense using B 1, B 2, or NB for all. Brazil was the base-case country. The model demonstrated that B 1 for those aged <70 years and B 2 for those ≥70 years were optimal for minimizing bed-days. Compared with NB, bed-days were reduced by 75%, hospital admissions by 68%, and intensive care unit admissions by 90%. Total costs were reduced by 60% with medical resource use reduced by 81%. This illustrates that the CO model can be used by healthcare decision-makers to implement vaccine booster allocation strategies that provide the best healthcare outcomes in a broad range of contexts.

Purpose: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 80%-90% of the cases. In Brazil, between 2018 and 2019, lung cancer was ranked as the second most frequent cancer among men and the fourth among women. The primary objectives were to describe the journey and survival rates of patients with advanced NSCLC treated in the Brazilian private health care system (HCS)., Materials and Methods: A retrospective cohort study was based on the search in administrative databases to analyze the Brazilian private HCS. Patients with advanced NSCLC diagnosed between 2011 and 2016 were included. The data on demographics, cancer-related information, treatment-related information, and resources used were collected. Survival analyses were performed using the semiparametric Kaplan-Meier method to assess mortality by NSCLC stage, with NSCLC diagnosis as the index date., Results: A total of 5,016 patients were included. Most patients were between 60 and 69 years old (33.6%) and had completed elementary school (52.2%). There was a greater proportion of men (58.1% v 41.9%), and the majority of patients had stage IV NSCLC (67%). It took an average of 31 days, from the first consultation, to have diagnosis. In 44% of the cases, a clinical oncologist was the first specialist in the HCS that the patient was referred to. After the diagnosis, the median time to start of treatment was 35 days. Chemotherapy alone was the most common treatment regimen (32%). The median overall survival was 11.5 months and 6 months for stage II and IV NSCLC, respectively., Conclusion: This study provides contemporary data on stage III and IV NSCLC in private health care in Brazil, which has shown a high rate of metastatic disease diagnoses, high health care-related costs, and low survival rates., Competing Interests: Marcia Datz AbadiEmployment: MSDLeadership: MSDStock and Other Ownership Interests: MSDResearch Funding: MSDTravel, Accommodations, Expenses: MSD Paula de Mendonça BatistaEmployment: MSD Fernando Brandão SerraEmployment: MSD LATAMLeadership: MSD LATAMStock and Other Ownership Interests: Merck Rodrigo Buzzatti PeixotoEmployment: MSD/MerckStock and Other Ownership Interests: Merck Lucas Miyake OkumuraEmployment: MAPESolutionsConsulting or Advisory Role: Novartis, Amgen, Bergamo, MSD, Pfizer, Libbs, TerumoSpeakers' Bureau: Novartis, Amgen, Bergamo, MSD, Pfizer, Libbs, TerumoResearch Funding: MSD, Pfizer, Libbs, TerumoTravel, Accommodations, Expenses: Novartis, Amgen, Bergamo, Libbs, Terumo Erica Regina CerqueiraEmployment: MSD OncologyStock and Other Ownership Interests: MSD OncologyTravel, Accommodations, Expenses: MSD OncologyNo other potential conflicts of interest were reported.

Background: A recent systematic review concluded that critically ill pediatric patients have higher odds of vancomycin-related nephrotoxicity [odds ratio (OR): 3.61, 95% CI: 1.21-10.74]. We aimed to assess the incidence and risk factors for vancomycin-associated nephrotoxicity in critically ill children without preexisting renal injury., Methods: A cohort of children admitted to a pediatric intensive care unit, from 2011 to 2016 treated with vancomycin without preexisting renal injury. The main diagnosis, therapeutic interventions and medications administered in this period were evaluated. Generalized estimating equation models were used to assess the association between clinical covariates and the dependent variable pediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE)., Results: Hundred ten patients, representing 1177 vancomycin days, were analyzed. Vancomycin-associated nephrotoxicity was seen in 11.8%. In a multivariate model, higher vancomycin doses were not associated with poorer renal function (P = 0.08). Higher serum vancomycin levels were weakly associated with pRIFLE classification (OR: 1.05, 95% CI: 1.02-1.07). Furosemide or amphotericin B in addition to the vancomycin treatment was associated with impaired renal function (OR: 2.56, 95% CI: 1.38-4.8 and OR: 7.7 95% CI: 2.55-23, respectively)., Conclusions: Vancomycin-associated nephrotoxicity in acute ill children without preexisting renal injury, measured with pRIFLE, is close to 11.8%. Furosemide and amphotericin B in addition to the vancomycin treatment are strong predictors of worse pRIFLE scores. The influence of acute kidney injury status at pediatric intensive care unit admission and the method used for renal function assessment might influence the incidence of vancomycin-associated nephrotoxicity and its associated risk factors.

An eight-year long case series follow-up study with pediatric bone cancer patients was conducted to compare the occurrence of adverse events associated with aprepitant with official sources of drug information (manufacturer's leaflet, clinical trials, and European Medicines Agency leaflet). All patients admitted were analyzed, representing 192 aprepitant cycles. Anorexia, febrile neutropenia, and headache were observed in frequencies over 43.8 per 100 patients, which was higher than previous estimates. Adverse events were classified as probable or possible, by using Naranjo score. The increased rates of adverse events, especially on the risk febrile neutropenia, warrant further safety studies on this population.

Objective: To report a case of a 4-month old girl that required 0.7 mg/kg/day (5 mg) of warfarin and discuss relevant risk factors for requiring higher doses., Case Description: In November 2015, a 5 kg female infant (36-week preterm) was admitted to the hospital due to status epilepticus and fever. Diazepam, phenytoin and ceftriaxone were prescribed. Cerebrospinal fluid contained 7 leukocytes, 150 mg/dL proteins, 1 mg/dL glucose and gram positive cocci were observed. Cranial tomography suggested hypodense signs in the cerebellum, right temporal lobe and left basal nuclei, which was consistent with pneumococcal meningitis-induced infectious vasculitis. She required low molecular weight heparin and warfarin for post-encephalitis thrombosis. About 10 days were required to achieve therapeutic INR, and warfarin was adjusted five times since the initial prescription., Comments: The risk factors for higher warfarin doses were age and enteral tube feeding. Phenobarbital and prednisone might also have contributed with one of the highest warfarin dose ever reported. Despite current importance given to genetics testing, clinicians should attempt to identify common contributing factors for prolonged non-therapeutic INR, to minimize the risk of coagulation, and to reduce costs of hospital stay and laboratory exams.

Aims: To review the efficacy and safety of aprepitant in combination with ondansetron and dexamethasone (triple therapy) in children and adolescents on moderate to highly emetogenic chemotherapy., Methods: Medline, Embase, Scielo, Lilacs, Cochrane and congress abstracts published until September 2016 were used as data sources. Two reviewers independently selected manuscripts and extracted data. A third reviewer solved discrepancies in study selection and data extraction. The primary outcome was overall complete response (no vomiting from 0 to 120 h). Secondary outcomes were: response in acute phase, delayed phase and reported toxicities. Each study was considered a unit of analysis. Summarized relative risks were recalculated based on reported data. All meta-analyses used a random-effects model and heterogeneity was reported using the I 2 method., Results: From 1004 studies, we screened 288 titles and abstracts and included three trials for data extraction. The population comprised 451 patients. Most patients were males, ranging from 6 months to 19 years of age, and weighing from 6 to 134 kg. Bone cancer was the most incident (≥50%) neoplasm, followed by rhabdomyosarcoma and Hodgkin's lymphoma. Triple therapy was associated with a reduced risk of developing chemotherapy-induced vomiting (CIV) (RR = 0.48; 95% CI 0.34-0.67). There were no differences in incidence of febrile neutropenia between groups (RR = 1.02; 95% CI 0.66-1.58)., Conclusions: Triple therapy decreased CIV risk, without increasing the occurrence of febrile neutropenia. However, this review could not address which subpopulations would most benefit from using this strategy. Future studies should focus on assessing risk factors for nausea and vomiting, as many patients did not achieve a complete antiemetic response., (© 2016 The British Pharmacological Society.)

Objective: Clinical Pharmacy Services (CPS) are considered standard of care and they are endorsed by the Joint Commission International, the American Academy of Pediatrics, and the American College of Clinical Pharmacy. In Brazil, single experiences have been discreetly arising and the importance of these services to children and adolescents care has led to interesting results, but certainly are under reported. This short report aims to discuss the effect of implementing a bedside CPS at a Brazilian Pediatric Intensive Care Unit (PICU)., Methods: This is a cross-sectional study conducted in a 12 bed PICU community hospital, from Campo Largo/Brazil. Subjects with<18 years old admitted to PICU were included for descriptive analysis if received a CPS intervention., Results: Of 53 patients accompanied, we detected 141 preventable drug-related problems (DRPs) which were solved within clinicians (89% acceptance of all interventions). The most common interventions performed to improve drug therapy included: preventing incompatible intravenous solutions (21%) and a composite of inadequate doses (17% due to low, high and non-optimized doses). Among the top ten medications associated with DRPs, five were antimicrobials. By analyzing the correlation between DRPs and PICU length of stay, we found that 74% of all variations on length of stay were associated with the number of DRPs., Conclusions: Adverse drug reactions due to avoidable DRPs can be prevented by CPS in a multifaceted collaboration with other health care professionals, who should attempt to use active and evidence-based strategies to reduce morbidity related to medications., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2016. Publicado por Elsevier Editora Ltda.)

Background Adherence to prescribed drug therapy is associated with lower rates of cardiovascular causes of death. In view of the relevance for public health, it is important to understand the relation between medication adherence tools' scores, especially in low literacy patients discharged from a cardiology ward. Objectives We aimed to assess: (a) the association between number of controlled clinical conditions and adherence tools scores, and (b) the correlation between the scores of three instruments to assess adherence. Methods We conducted a prospective study and included patients discharged from a specialized cardiovascular ward in Brazil. The results of the Beliefs about Medicines questionnaire (BMQ), the Adherence to Refills and Medication Scale (ARMS) and the MedTake test were compared. Results Of 53 included patients, most of them were elderly, and did not complete primary school. On average, there were six health conditions per patient, where two of them were not controlled. ARMS was the only tool that was associated with number of controlled health conditions (r = -0.312, p < 0.05). Moreover, ARMS (average score 15.6 ± 3.4) had significant correlation with MEDTAKE (r = 0.535, p < 0.01) and BMQ (r = 0.38, p < 0.01). BMQ and MEDTAKE were also positively correlated (r = 0.311, p < 0.05). Conclusions Clinically, higher ARMS scores (>12) suggest assumed non-adherence. It is also negatively correlated with the number of controlled clinical conditions in low literacy elderlies with cardiovascular diseases.

There is a lack of formal economic analysis to assess the efficiency of antimicrobial stewardship programs. Herein, we conducted a cost-effectiveness study to assess two different strategies of Antimicrobial Stewardship Programs. A 30-day Markov model was developed to analyze how cost-effective was a Bundled Antimicrobial Stewardship implemented in a university hospital in Brazil. Clinical data derived from a historical cohort that compared two different strategies of antimicrobial stewardship programs and had 30-day mortality as main outcome. Selected costs included: workload, cost of defined daily doses, length of stay, laboratory and imaging resources used to diagnose infections. Data were analyzed by deterministic and probabilistic sensitivity analysis to assess model's robustness, tornado diagram and Cost-Effectiveness Acceptability Curve. Bundled Strategy was more expensive (Cost difference US$ 2119.70), however, it was more efficient (US$ 27,549.15 vs 29,011.46). Deterministic and probabilistic sensitivity analysis suggested that critical variables did not alter final Incremental Cost-Effectiveness Ratio. Bundled Strategy had higher probabilities of being cost-effective, which was endorsed by cost-effectiveness acceptability curve. As health systems claim for efficient technologies, this study conclude that Bundled Antimicrobial Stewardship Program was more cost-effective, which means that stewardship strategies with such characteristics would be of special interest in a societal and clinical perspective., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Objectives: To assess a bundled Antimicrobial Stewardship Program and its effect on mortality., Data: Eight months of clinical electronic medical records and Antimicrobial Stewardship Program registries were used as source of data., Method: This is a historical cohort study conducted in a Brazilian University Hospital. Eligible patients were admitted to general wards or intensive care units and had an antimicrobial therapy prescribed and assessed by different strategies: Bundled Antimicrobial Stewardship Program (bundled intervention consisted of clinical pharmacist chart review, discussion with microbiologist and infectious disease physicians, local education and continuous follow-up) or Conventional Antimicrobial Stewardship Program (clinical pharmacist chart review and discussion with infectious disease physician). Primary outcome from this study was 30-day mortality, which was compared between groups, by using Kaplan-Meier survival curve and log-rank test. Other outcomes included Defined Daily Doses per 1000 patient-days and occurrence of resistant bacteria., Results: From 533 patients, 491 were eligible for the study, of which 191 patients were included to Antimicrobial Stewardship Program and 300 to Conventional strategy. In general, they were likely to be male and age was similar in groups (58.9 vs 55.5 years, p=0.38). Likewise, Charlson Comorbidity Index was not statistically different between groups (2.6 vs 2.7, p=0.2). Bloodstream site infections were frequently diagnosed in both groups (30.89% vs 26%, p=0.24). Other less common sites of infections were central nervous system and lungs. The ASP group had higher survival rates (p<0.01) and the risk difference was 10.8% (95% CI: 2.41-19.14). There were less Defined Daily Doses per 1000 patient-days (417 vs 557.2, p<0.05) and higher rates of resistant bacteria identified in the ASP group (83% vs 17%)., Conclusion: Bundled ASP was the most effective strategy, with reduced mortality and Defined Daily Doses per 1000 patient-days., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

Background Pharmacists' counseling has improved health-related outcomes in many acute and chronic conditions. Several studies have shown how pharmacists have been contributing to reduce morbidity and mortality related to drug-therapy (MMRDT). However, there still is a lack of reviews that assemble evidence-based clinical pharmacists' counseling. Equally, there is also a need to understand structure characteristics, processes and technical contents of these clinical services. Aim of the review To review the structure, processes and technical contents of pharmacist counseling or education reported in randomized controlled trials (RCT) that had positive health-related outcomes. Methods We performed a systematic search in specialized databases to identify RCT published between 1990 and 2013 that have evaluated pharmacists' counseling or educational interventions to patients. Methodological quality of the trials was assessed using the Jadad scale. Pharmacists' interventions with positive clinical outcomes (p < 0.05) were evaluated according to patients' characteristics, setting and timing of intervention, reported written and verbal counseling. Results 753 studies were found and 101 RCT matched inclusion criteria. Most of the included RCTs showed a Jadad score between two (37 studies) and three (32 studies). Pharmacists were more likely to provide counseling at ambulatories (60 %) and hospital discharge (25 %); on the other hand pharmacists intervention were less likely to happen when dispensing a medication. Teaching back and explanations about the drug therapy purposes and precautions related to its use were often reported in RCT, whereas few studies used reminder charts, diaries, group or electronic counseling. Most of studies reported the provision of a printed material (letter, leaflet or medication record card), regarding accessible contents and cultural-concerned informations about drug therapy and disease. Conclusion Pharmacist counseling is an intervention directed to patients' health-related needs that improve inter-professional and inter-institutional communication, by collaborating to integrate health services. In spite of reducing MMRDT, we found that pharmacists' counseling reported in RCT should be better explored and described in details, hence collaborating to improve medication-counseling practice among other countries and settings.

In mice, successful development and reproduction require that all cells, including germ cells, transition from a pluripotent to a differentiated state. This transition is associated with silencing of the pluripotency genes Oct4 and Nanog. Interestingly, these genes are repressed at different developmental timepoints in germ and somatic cells. Ovarian germ cells maintain their expression until about embryonic day (E) 14.5, whereas somatic cells silence them much earlier, at about E8.0. In both somatic cells and embryonic stem cells, silencing of Oct4 and Nanog requires the nuclear receptor GCNF. However, expression of the Gcnf gene has not been investigated in fetal ovarian germ cells, and whether it is required for silencing Oct4 and Nanog in that context is not known. Here we demonstrate that Gcnf is expressed in fetal ovarian germ cells, peaking at E14.5, when Oct4 and Nanog are silenced. However, conditional ablation of the ligand-binding domain of Gcnf using a ubiquitous, tamoxifen-inducible Cre indicates that Gcnf is not required for the down-regulation of pluripotency genes in fetal ovarian germ cells, nor is it required for initiation of meiosis and oogenesis. These results suggest that the silencing of Oct4 and Nanog in germ cells occurs via a different mechanism from that operating in somatic cells during gastrulation.

In mammals, both testis and ovary arise from a sexually undifferentiated precursor, the genital ridge, which first appears during mid-gestation as a thickening of the coelomic epithelium on the ventromedial surface of the mesonephros. At least four genes (Lhx9, Sf1, Wt1, and Emx2) have been demonstrated to be required for subsequent growth and maintenance of the genital ridge. However, no gene has been shown to be required for the initial thickening of the coelomic epithelium during genital ridge formation. We report that the transcription factor GATA4 is expressed in the coelomic epithelium of the genital ridge, progressing in an anterior-to-posterior (A-P) direction, immediately preceding an A-P wave of epithelial thickening. Mouse embryos conditionally deficient in Gata4 show no signs of gonadal initiation, as their coelomic epithelium remains a morphologically undifferentiated monolayer. The failure of genital ridge formation in Gata4-deficient embryos is corroborated by the absence of the early gonadal markers LHX9 and SF1. Our data indicate that GATA4 is required to initiate formation of the genital ridge in both XX and XY fetuses, prior to its previously reported role in testicular differentiation of the XY gonad., Competing Interests: The authors have declared that no competing interests exist.