Building an antimicrobial stewardship program: A narrative of six years under the Donabedian perspective.

Introduction: Antimicrobial resistance (AMR) is increasing and represents one of the world's major challenges. AMR increase morbimortality, length of hospital stay and costs. Antimicrobial Stewardship Programs (ASP) are one of the key strategies to promote the rational use of antimicrobials since AMR is mostly driven by antimicrobial consumption. Objective: To describe the ASP implementation in a teaching hospital from the perspective of Donabedian quality assessment and the Brazilian regulatory requirements. Method: This was a descriptive study with secondary data collection, including document review of the ASP. The study setting was a general public 392-bed hospital. The ASP activities were performed by the hospital infection control committee (HICC), hospital pharmacy (HP) and diagnostic support laboratory (DSL). The description of the three services mainly involved in the ASP was based on a quality assessment model involving the dimensions of "structure", "process" and "result" proposed by Donabedian. The distribution among dimensions was guided by the checklist of essential elements of the ASP that compose the Brazilian regulatory requirements. The checklist was applied in July, 2022, and the ASP results described from 2016 to 2021. Results: ASP actions have been gradually implemented since 2008 with the implementation of HICC and improved over the years. Regarding structure, the investments in technology were mapped, quantifying 26 computers and three software programs employed to computerize the ASP processes performed in specific physical areas by HICC, HP and DSL. Institutional guidelines used by HICC, HP and DSL guided clinical practices to operationalize ASP. The evaluation metrics improved for 10 indicators and worsened for four indicators. From the 60 items composing the checklist, the hospital met the requirements in 73.3% of the items (n = 44). Conclusion: This study described the implementation of ASP in a teaching hospital, applying the Donabedian perspective. Although the hospital still does not have a classic ASP model, there were investments to improve structure, processes and results, aiming to comply with international guidelines. A high proportion of key elements of ASP in the hospital were followed according to the Brazilian regulatory requirements. Aspects related to antimicrobial consumption and the emergence of microbial resistance deserve further investigations.

Working Memory and Manual Dexterity in Dyslexic Children: A Systematic Review and Meta-Analysis.

Dyslexic children have impairments in working memory and manual dexterity. Studies have shown that when cognitive development has deficits, motor development is often impaired, indicating a strong interconnection between both domains, and the possibility of interference with each other's proper functioning. Thus, a new literature review is necessary to understand which components of working memory and manual dexterity are affected in dyslexic children and the possible relationship between them. This review aimed to perform a systematic review and meta-analysis to analyze both skills in dyslexic children. The protocol was carried out according to the criteria established by PRISMA being registered at PROSPERO under number CRD 42021238901. Six literature databases were searched to locate studies published between 2001 and 2021: EMBASE, ERIC, ISI Web of Science, PubMed, PsycINFO, and Scopus. 21 studies met the inclusion criteria. The findings suggest that dyslexic children have significantly poorer visuospatial and verbal working memory with more impairments in the phonological loop. No significant differences were found in manual dexterity.

Factors associated with nonadherence to the use of coumarin derivatives or direct oral anticoagulants: A systematic review of observational studies.

Nonadherence to thromboprophylaxis treatment with oral anticoagulants (OAC) is a public health problem and may be associated with high mortality rates. We sought to synthesize the factors associated with nonadherence to therapy with coumarin derivatives or direct oral anticoagulants. A systematic review was performed at electronic databases Medline, Embase, CINAHL, Lilacs and grey literature (Google Scholar, MedNar, OpenGray, ProQuest Dissertations and Theses, and hand search). This study was conducted according to Cochrane's method and PRISMA. The registration on PROSPERO is CRD42020223555. Overall, 1270 studies were identified and nine studies were selected for this review. In hand searching, 77 studies were found, but none included. The associated factors with nonadherence were heterogeneous, and some factors were described as both risk and protection for nonadherence, with few variables showing consistent results among the studies. Variables reported only as risk factors were "male sex", "hospitalization", "Charlson score" and "bleeding", while "white race", CHA2 DS2 VASc (score range 2-9)" and "polypharmacy" were reported only as protective factors. Most studies did not present details in the description of concepts and methods to assess nonadherence. In clinical practice, the knowledge on factors associated with nonadherence is helpful to identifying patients at higher risk of complications that would benefit from individualized interventions.

Systematic review of host genetic association with Covid-19 prognosis and susceptibility: What have we learned in 2020?

Biomarker identification may provide strategic opportunities to understand disease pathophysiology, predict outcomes, improve human health, and reduce healthcare costs. The highly heterogeneous Covid-19 clinical manifestation suggests a complex interaction of several different human, viral and environmental factors. Here, we systematically reviewed genetic association studies evaluating Covid-19 severity or susceptibility to SARS-CoV-2 infection following PRISMA recommendations. Our research comprised papers published until December 31st , 2020, in PubMed and BioRXiv databases focusing on genetic association studies with Covid-19 prognosis or susceptibility. We found 20 eligible genetic association studies, of which 11 assessed Covid-19 outcome and 14 evaluated infection susceptibility (five analyzed both effects). Q-genie assessment indicated moderate quality. Five large-scale association studies (GWAS, whole-genome, or exome sequencing) were reported with no consistent replication to date. Promising hits were found on the 3p21.31 region and ABO locus. Candidate gene studies examined ACE1, ACE2, TMPRSS2, IFITM3, APOE, Furin, IFNL3, IFNL4, HLA, TNF-ɑ genes, and ABO system. The most evaluated single locus was the ABO, and the most sampled region was the HLA with three and five candidate gene studies, respectively. Meta-analysis could not be performed. Available data showed the need for further reports to replicate claimed associations.

Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects.

Warfarin exhibits a wide variation in dose requirements. We sought to evaluate the association of polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) and nongenetic factors with maintenance doses of warfarin <17.5 mg/week and to create an algorithm to predict drug sensitivity. This is a retrospective cohort study including 312 patients assisted at an anticoagulation clinic in Brazil. The mean age of participants was 60.4 ± 13.5 years and 59.9% were female. The logistic regression model included: age [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06], genotype VKORC1 AA (OR 31.61, 95% CI 11.20-100.15) and genotype CYP2C9 2/2, 2/3 or 3/3 (OR 16.48, 95% CI 3.37-81.79). The creation of our algorithm involved warfarin-experienced patients on stable doses, identifying factors associated with drug sensitivity. The validation of this algorithm allows its use in future populations to determine the initial dose distinguishing patients with dose requirements <17.5 mg and reducing time to achieve stable doses.

Sociodemographic characteristics, clinical factors, and genetic polymorphisms associated with Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) has a multifactorial etiology involving an interaction of genetic and environmental factors. The Apolipoprotein E ε4 (ApoE ε4) is the single most important genetic risk factor for sporadic AD. Our aim was to study the association between sociodemographic, clinical data and gene polymorphisms in patients with sporadic AD in a heterogeneous genomic Brazilian population with low educational levels. METHODS: We selected 169 sporadic AD patients and 97 controls older than 65 years and compared co-variables between them: age, years of education, vascular risk factors, genomic ancestry, and functional polymorphisms of ApoE, BDNF, COMT, and 5-HTTLPR. We also determined the genomic ancestry of all individuals. RESULTS: The average years of education was significantly smaller in the patient's group (p = 0.003), and they had a history of depression when compared with controls (p < 0.001). The carriers of ApoE ε4 have an earlier onset of the disease (76.9 years) (p = 0.001) than ApoE ε3 (79.5 years) (p = 0.024). Patients with Met allele of Val66Met have a tendency to later onset of disease (p = 0.056). There were no differences in the genomic ancestry between groups. CONCLUSION: Low level of education and history of depression were associated with AD. Public policies and intensive observation of old-age patients with lifetime history of depression, especially APOE ε4 carriers, could improve the well-being of our population.