Clinical auditory alarms are often found in hospital wards and operating rooms. In these environments, regular daily tasks can result in having a multitude of concurrent sounds (from staff and ...patients, building systems, carts, cleaning devices, and importantly, patient monitoring devices) which easily amount to a prevalent cacophony. The negative impact of this soundscape on staff and patients' health and well-being, as well as in their performance, demand for accordingly designed sound alarms. The recently updated IEC60601-1-8 standard, in guidance for medical equipment auditory alarms, proposed a set of pointers to distinctly convey medium or high levels of priority (urgency). However, conveying priority without compromising other features, such as ease of learnability and detectability, is an ongoing challenge. Electroencephalography, a non-invasive technique for measuring the brain response to a given stimulus, suggests that certain Event-Related Potentials (ERPs) components such as the Mismatch Negativity (MMN) and P3a may be the key to uncovering how sounds are processed at the pre-attentional level and how they may capture our attention. In this study, the brain dynamics in response to the priority pulses of the updated IEC60601-1-8 standard was studied via ERPs (MMN and P3a), for a soundscape characterised by the repetition of a sound (generic SpO2 "beep"), usually present in operating and recovery rooms. Additional behavioural experiments assessed the behavioural response to these priority pulses. Results showed that the Medium Priority pulse elicits a larger MMN and P3a peak amplitude when compared to the High Priority pulse. This suggests that, at least for the applied soundscape, the Medium Priority pulse is more easily detected and attended at the neural level. Behavioural data supports this indication, showing significantly shorter reaction times for the Medium Priority pulse. The results pose the possibility that priority pointers of the updated IEC60601-1-8 standard may not be successfully conveying their intended priority levels, which may not only be due to design properties but also to the soundscape in which these clinical alarms are deployed. This study highlights the need for intervention in both hospital soundscapes and auditory alarm design settings.
Objectives
The emergency department (ED) is a very important healthcare entrance point, known for its challenging organisation and management due to demand unpredictability. An accurate forecast ...system of ED visits is crucial to the implementation of better management strategies that optimise resources utilization, reduce costs and improve public confidence. The aim of this review is to investigate the different factors that affect the ED visits forecasting outcomes, in particular the predictive variables and type of models applied.
Methods
A systematic search was conducted in PubMed, Web of Science and Scopus. The review methodology followed the PRISMA statement guidelines.
Results
Seven studies were selected, all exploring predictive models to forecast ED daily visits for general care. MAPE and RMAE were used to measure models' accuracy. All models displayed good accuracy, with errors below 10%.
Conclusions
Model selection and accuracy was found to be particularly sensitive to the ED dimension. While ARIMA‐based and other linear models have good performance for short‐time forecast, some machine learning methods proved to be more stable when forecasting multiple horizons. The inclusion of exogenous variables was found to be advantageous only in bigger EDs.
Highlights
This work provides an insight into the study of forecasting emergency department (ED) visits, exploring different methodologies.
Through the extracted data, it sets a unique analysis on how study features affect model's performance.
It establishes a baseline knowledge for future studies that aim to explore these models.
These forecasting models are important for hospital resource management planning.
Abnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (
HOTAIR
) is oncogenic in several human cancers, including gliomas. The
HOTAIR
single nucleotide polymorphisms ...(SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of
HOTAIR
, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these
HOTAIR
SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and
HOTAIR
expression levels, while rs12826786 CT genotype was associated with increased intratumoral
HOTAIR
RNA levels when compared to TT genotype (
p
-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that
HOTAIR
SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.
Background Antimicrobial resistance remains a major global public health concern, and antimicrobial dispensing in community pharmacies is an important factor in preventing this damage. However, the ...current literature focuses on the technical and attitudinal aspects related to antimicrobial dispensing, with little emphasis on the interventions provided in this service. Thus, this study aimed to determine the antimicrobial dispensing process in community pharmacies. Methods A scoping review was performed in September 2020 using the PubMed, EMBASE, LILACS, Web of Science, and Cochrane databases. The search terms included words related to dispensing, antibacterial agents, and pharmacies in various combinations. Two reviewers screened the titles, abstracts, and full-text articles according to the eligibility criteria, and extracted the data. The findings were presented in a descriptive form. Results Of the 7713 studies screened, 35 were included, of which 22 (63%) were published in Asia. Most studies followed a cross-sectional design (n = 27), and the simulated patient was the most often used method to assess the antimicrobial dispensing process (n = 22). Moreover, 31 (89%) studies investigated antimicrobial dispensing without prescription, and only four (11%) studies evaluated antimicrobial dispensing with prescription. In the 35 studies, the most frequently asked questions were about drug allergies (n = 19) and patient symptoms (n = 18), and counseling mainly focused on the side effects (n = 14), precautions (n = 14), how to take the medication (n = 12), and duration of medication use (n = 11). Another common intervention was referral (n = 15). Among clinical cases, counseling on medication use occurred often in cases of urinary tract infection (51%) and otitis media (50%). Conclusions Antimicrobial dispensing processes have been primarily investigated in low- and middle-income countries, with a focus on dispensing antimicrobials without prescriptions. During the dispensing process, pharmacists mostly posed minimal questions and counseling, highlighting the deficiencies that persist in this practice. Our results indicate the need for multifaceted strategies, such as implementing educational, regulatory or administrative strategies and changes in cultural background, especially in low- and middle-income countries, that aim to reduce indiscriminate use of antimicrobials. Therefore, qualifying the antimicrobial dispensing process is a fundamental factor for improving the rational use of antimicrobials and reducing microbial resistance. Keywords: Antimicrobials, Dispensing, Community pharmacy, Pharmacists
Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a ...significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing. However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria.
We evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute in real-world clinical practice.
Of the 25 patients, 76% discontinued therapy in sustained deep molecular response (SDMR) and 24% were in unsustained DMR (UDMR). Discontinuation of therapy due to adverse effects was observed in 5 and 50% of the patients in the SDMR and UDMR groups, respectively. After TKI discontinuation, patients were followed for a median of 24 months. At the time of this analysis, 56% patients had a molecular relapse after a median of 4 months. SDMR and longer treatment duration were associated with lower probability of molecular relapse: 25% in SDMR patients with TKI treatment > 96 months and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least major molecular response (MMR).
Our results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer TKI treatment duration.
Currently, two conventional freezing techniques are used in sperm cryopreservation: slow freezing (SF) and rapid freezing (RF). Despite the protocolar improvements, cryopreservation still induces ...significant alterations in spermatozoon that are poorly understood. Here, available proteomic data from human cryopreserved sperm was analyzed through bioinformatic tools to unveil key differentially expressed proteins (DEPs) that can be used as modulation targets or quality markers. From the included proteomic studies, 160 and 555 DEPs were collected for SF and RF groups, respectively. For each group, an integrative network was constructed using gene ontology and protein-protein interaction data to identify key DEPs. Among them, arylsulfatase A (ARSA) was highlighted in both freezing networks, and low ARSA levels have been associated with poor-sperm quality. Thus, ARSA was selected for further experimental investigation and its levels were assessed in cryopreserved samples by western blot. ARSA levels were significantly decreased in RF and SF samples (∼31.97 and ∼39.28%, respectively). The bioinformatic analysis also revealed that the DEPs were strongly associated with proteasomal and translation pathways. The purposed bioinformatic approach allowed the identification of potential key DEPs in freeze-thawed human spermatozoa. ARSA has the potential to be used as a marker to assess sperm quality after cryopreservation.
Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of ...chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line.
Altered glycolytic metabolism has been associated with chemoresistance in acute myeloid leukemia (AML). However, there are still aspects that need clarification, as well as how to explore these ...metabolic alterations in therapy. In the present study, we aimed to elucidate the role of glucose metabolism in the acquired resistance of AML cells to cytarabine (Ara-C) and to explore it as a therapeutic target. Resistance was induced by stepwise exposure of AML cells to increasing concentrations of Ara-C. Ara-C-resistant cells were characterized for their growth capacity, genetic alterations, metabolic profile, and sensitivity to different metabolic inhibitors. Ara-C-resistant AML cell lines, KG-1 Ara-R, and MOLM13 Ara-R presented different metabolic profiles. KG-1 Ara-R cells exhibited a more pronounced glycolytic phenotype than parental cells, with a weaker acute response to 3-bromopyruvate (3-BP) but higher sensitivity after 48 h. KG-1 Ara-R cells also display increased respiration rates and are more sensitive to phenformin than parental cells. On the other hand, MOLM13 Ara-R cells display a glucose metabolism profile similar to parental cells, as well as sensitivity to glycolytic inhibitors. These results indicate that acquired resistance to Ara-C in AML may involve metabolic adaptations, which can be explored therapeutically in the AML patient setting who developed resistance to therapy.
The indiscriminate use of antimicrobials is considered a major contributing factor to the increase in antimicrobial resistance. Community pharmacies are the main source of access to antimicrobials, ...and pharmacists are in a strategic position to promote rational use of these medicines. Therefore, it is important to know dispensing service quality.
To evaluate the behavior of pharmacists in dispensing antimicrobials in community pharmacies in northeast Brazil.
This cross-sectional pilot study was conducted from August to October 2021 in a private community pharmacy chain in Sergipe. Dispensing was evaluated using the simulated patient (SP) technique. Two SP asked the pharmacists for the antimicrobials (case clinic 1: upper respiratory infection; case clinic 2: urinary tract infection) and recorded the service through audio. Dispensing practices were independently analyzed by two researchers based on the tools available in the literature. Data were presented using descriptive statistics.
A total of 54 simulated patient visits were conducted. Based on the 12 steps recommended by the research team for good dispensing, pharmacists asked an average of 1 (±1.17) question for upper respiratory infections and 0.3 (±0.54) for urinary tract infections, as well as provided counseling (mean number of recommendations, 2.6 (±1.44) and 4.5 (±2.35), respectively). As for communication skills, pharmacists had a regular score (3.07 ± 0.34). Furthermore, there was no significant difference in the number of steps and counseling recommendations by pharmacists in dispensing clinical cases 1 and 2 (p = 0.0674).
The quality of antimicrobial dispensing was evaluated as suboptimal, requiring improvements in practice and multifaceted strategies to promote continuing education of these professionals. In addition, awareness actions for the population must be implemented to promote the rational use of antimicrobials and reduce microbial resistance.
Drug dispensing aims to promote rational medicine use. However, in many countries, the work processes are still not well defined. In this sense, the perception of pharmacists about dispensing ...practices presents an overview of how the service is being performed in the country and its main challenges. Thus, the purpose of this study was to determine the self-reported work process of Brazilian community pharmacists in relation to drug dispensing, challenges, and strategies for carrying out the service.
A cross-sectional survey was conducted between May and July 2021, with community pharmacists from all regions of Brazil. Pharmacists were invited to answer a validated, self-administered questionnaire, implemented through Google Forms, containing 33 questions related to the steps of drug dispensing (questions and counseling) and the main challenges and strategies to perform the service. The data were exported to Microsoft Office Excel and SPSS®. Multiple linear regression analysis was used to assess the association between responses and demographic information, with a significance level of less than 5% (p < 0.05). This study was approved by the Research Ethics Committee (number: 4.295.171).
A total of 625 community pharmacists responded to the survey. Most pharmacists reported always or frequently performing 17 (54%) of the 31 steps described in the instrument. The steps that pharmacists reported performing more frequently were forming the medication name (n = 569, 91.04%), verifying the completeness and adequacy of the prescription according to current legislation (n = 567, 90.72%) and providing counseling on dosage (n = 549, 87.84%). Documentation was the main step in which pharmacists reported never or rarely performing (n = 424, 67.84%). The results showed that there was a significant influence of the variables of public education institution, age, and postgraduate education on the frequency of dispensing steps (F(3, 621) = 14.884, p < 0.001; R
= 0,063).
This study showed that most pharmacists reported always or frequently asking most of the questions and performing counseling contained in the instrument during drug dispensing. These results can contribute to an understanding of current dispensing practices and generate insights for developing strategies to qualify the service.
PDF
