Pharmacotherapy assessment and adverse drug reactions in older patients admitted to intensive care.

INTRODUCTION: Older patients are more susceptible to medication use, and physiological changes resulting from aging and organic dysfunctions presented by critically ill patients may alter the pharmacokinetic or pharmacodynamic behavior. Thus, critically ill older people present greater vulnerability to the occurrence of pharmacotherapeutic problems. OBJECTIVE: To evaluate pharmacotherapy and the development of potential adverse drug reactions (ADRs) in older patients admitted to an intensive care unit (ICU). METHOD: A cohort study was conducted in an ICU for adults of a Brazilian University Hospital during a 12-month period. The patients' pharmacotherapy was evaluated daily, considering the occurrence of ADRs and drug-drug interactions (DDIs), the use of potentially inappropriate medications (PIMs) for older people, and the pharmacotherapy anticholinergic burden (ACB). A trigger tool was used for active search of ADRs, with subsequent causality evaluation. PIM use was evaluated by means of the Beers criteria and the STOPP/START criteria. The ABC scale was employed to estimate ACB. The Micromedex® and Drugs.com® medication databases were employed to evaluate the DDIs. RESULTS: The sample of this study consisted of 41 patients, with a mean age of 66.8 years old (±5.2). The 22 triggers used assisted in identifying 15 potential ADRs, and 26.8% of the patients developed them. The mean estimated ACB score was 3.0 (±1.8), and the patients used 3.1 (±1.4) and 3.3 (±1.6) PIMs according to the Beers and the STOPP criteria, respectively. A total of 672 DDIs were identified, with a mean of 16.8 (±9.5) DDIs/patient during ICU hospitalization. Our findings show an association between occurrence of ADRs in the ICU and polypharmacy (p=.03) and DDIs (p=.007), corroborating efforts for rational medication use as a preventive strategy. CONCLUSIONS: Using tools to evaluate the pharmacotherapy for older people in intensive care can assist in the recognition and prevention of pharmacotherapeutic problems, with emphasis on the identification of ADRs through the observation of triggers and subsequent causality analysis.

Analysis of clinical outcomes in older individuals who received pharmaceutical care and posthospital discharge follow-up.

BACKGROUND: Previous evidence underscores the need to assess potential clinical outcomes resulting from pharmaceutical care interventions and to monitor patient's progress to evaluate their clinical evolution, which is crucial for bolstering the relevance of implementing pharmaceutical care in healthcare services. AIMS: To conduct an in-depth analysis of pharmaceutical care practices in a geriatric ward and monitor the clinical outcomes of older people served. METHODS: This interventionist study was conducted in the geriatrics ward of a Brazilian university hospital. The research intervention occurred between January and May 2022, with a follow-up conducted for up to 90 days after patients' hospital discharge. Older patients in the geriatrics ward received pharmaceutical care, including medication reconciliation, medication review, and pharmacotherapeutic follow-up, aimed at identifying and resolving drug-related problems (DRPs). The clinical relevance of DRPs and pharmaceutical recommendations was evaluated. Additionally, analyses were conducted on mortality and rehospitalization outcomes in older patients at 30, 60, and 90 days following initial hospital discharge. RESULTS: Of the patients evaluated, a significant 88.3% exhibited at least one DRP (with an average of 2.6 ± 1.9 DRPs per patient), with the majority classified as need/indication problems (38.9%). The acceptance rate of pharmaceutical recommendations was 80.9%, with the majority categorized as very significant relevance (60.4%). DRPs were predominantly of serious clinical relevance (50.9%). In patients whose clinical indicators could be monitored, 95.5% showed some clinical response (in vital signs, laboratory tests and/or clinical status evolution) potentially related to resolved DRPs. Association analysis revealed that a higher number of medications in use before hospitalization correlated with a greater identification of DRPs during hospitalization (p = 0.03). At hospital discharge, 23.6% of patients were no longer using polypharmacy. In total, 16 patients (26.7%) died during the study period. Among patients who did not die during hospitalization (n = 54), 20 patients (37%) experienced rehospitalizations within 90 days following discharge. CONCLUSION: This study facilitated the consolidation of pharmaceutical care implementation in a geriatric ward. We conducted identification, evaluation, and proposed evidence-based solutions, as well as monitored cases for outcome analysis. It is anticipated that this methodology will inspire future research and the implementation of pharmaceutical care-related services.

Satellite DNAs, heterochromatin, and sex chromosomes of the wattled jacana (Charadriiformes; Jacanidae): a species with highly rearranged karyotype.

Charadriiformes, which comprises shorebirds and their relatives, is one of the most diverse avian orders, with over 390 species showing a wide range of karyotypes. Here, we isolated and characterized the whole collection of satellite DNAs (satDNAs) at both molecular and cytogenetic levels of one of its representative species, named the wattled jacana (Jacana jacana), a species that contains a typical ZZ/ZW sex chromosome system and a highly rearranged karyotype. In addition, we also investigate the in situ location of telomeric and microsatellite repeats. A small catalog of 11 satDNAs was identified that typically accumulated on microchromosomes and on the W chromosome. The latter also showed a significant accumulation of telomeric signals, being (GA)10 the only microsatellite with positive hybridization signals among all the 16 tested ones. These current findings contribute to our understanding of the genomic organization of repetitive DNAs in a bird species with high degree of chromosomal reorganization contrary to the majority of bird species that have stable karyotypes.

Validated medication deprescribing instruments for patients with palliative care needs palliative care: A systematic review. / [Artículo traducido] Instrumentos validados de desprescripción de medicamentos para los pacientes con necesidades de cuidados paliativos: una revisión sistemática.

OBJECTIVES: Patients with life-limiting illnesses are prone to unnecessary polypharmacy. Deprescribing tools may contribute to minimizing negative outcomes. Thus, the aims of the study were to identify validated instruments for deprescribing inappropriate medications for patients with palliative care needs and to assess the impact on clinical, humanistic, and economic outcomes. METHODS: A systematic review was conducted in LILACS, PUBMED, EMBASE, COCHRANE, and WEB OF SCIENCE databases (until May 2021). A manual search was performed in the references of enrolled articles. The screening, eligibility, extraction, and bias risk assessment were carried out by two independent researchers. Experimental and observational studies were eligible for inclusion. RESULTS: Out of the 5,791 studies retrieved, after excluding duplicates (n = 1,050), conducting title/abstract screening (n = 4,741), and full reading (n = 41), only one study met the inclusion criteria. In this included study, a randomized controlled trial was conducted, which showed a high level of bias risk overall. Adults 75 years or older (n = 130) with limited life expectancy and polypharmacy were allocated to two groups [intervention arm (deprescribing); and control arm (usual care)]. Deprescribing was performed with the aid of the STOPPFrail tool. The mean number of inappropriate medications and monthly medication costs were significantly lower in the intervention arm. No statistically significant differences were found in terms of unscheduled hospital presentations, falls, fractures, mortality, and quality of life. CONCLUSIONS: Despite the availability of several instruments to support deprescribing in patients with palliative care needs, only one of them has undergone validation and robust assessment for effectiveness in clinical practice. The STOPPFrail tool appears to reduce the number of inappropriate medications for older people with limited life expectancy (and probably palliative care needs) and decrease the monthly costs of pharmacotherapy. Nevertheless, the impact on patient safety and humanistic outcomes remain unclear.

Validated medication deprescribing instruments for patients with palliative care needs: a systematic review.

OBJECTIVES: Patients with life-limiting illnesses are prone to unnecessary polypharmacy. Deprescribing tools may contribute to minimizing negative outcomes. Thus, the aims of the study were to identify validated instruments for deprescribing inappropriate medications for patients with palliative care needs and to assess the impact on clinical, humanistic, and economic outcomes. METHODS: A systematic review was conducted in LILACS, PUBMED, EMBASE, COCHRANE, and WEB OF SCIENCE databases (until May 2021). A manual search was performed in the references of enrolled articles. The screening, eligibility, extraction, and bias risk assessment were carried out by 2 independent researchers. Experimental and observational studies were eligible for inclusion. RESULTS: Out of the 5791 studies retrieved, after excluding duplicates (n = 1050), conducting title/abstract screening (n = 4741), and full reading (n = 41), only 1 study met the inclusion criteria. In this included study, a randomized controlled trial was conducted, which showed a high level of bias risk overall. Adults 75 years or older (n = 130) with limited life expectancy and polypharmacy were allocated to 2 groups [intervention arm (deprescribing); and control arm (usual care)]. Deprescribing was performed with the aid of the STOPPFrail tool. The mean number of inappropriate medications and monthly medication costs were significantly lower in the intervention arm. No statistically significant differences were found in terms of unscheduled hospital presentations, falls, fractures, mortality, and quality of life. CONCLUSIONS: Despite the availability of several instruments to support deprescribing in patients with palliative care needs, only 1 of them has undergone validation and robust assessment for effectiveness in clinical practice. The STOPPFrail tool appears to reduce the number of inappropriate medications for older people with limited life expectancy (and probably palliative care needs) and decrease the monthly costs of pharmacotherapy. Nevertheless, the impact on patient safety and humanistic outcomes remain unclear.

Flow through Deformed Carbon Nanotubes Predicted by Rigid and Flexible Water Models.

In this study, using nonequilibrium molecular dynamics simulation, the flow of water in deformed carbon nanotubes is studied for two water models TIP4P/2005 and simple point charge/FH (SPC/FH). The results demonstrated a nonuniform dependence of the flow on the tube deformation and the flexibility imposed on the water molecules, leading to an unexpected increase in the flow in some cases. The effects of the tube diameter and pressure gradient are investigated to explain the abnormal flow behavior with different degrees of structural deformation.

A Review of Software and Mobile Apps to Support the Clinical Diagnosis of Hansen Disease.

This scoping review indicates a lack of scientific articles that specifically explore software and mobile applications designed to assist in the clinical diagnosis of leprosy, and our findings have provided insights into the available tools, their usage methods, and the benefits offered by health technologies.

Experiences and strategies adopted for the implementation of pharmaceutical services in hospital geriatric units: A scoping review protocol.

Background: Pharmaceutical care is considered an important pillar for promoting the rational and safe use of medicines. Consequently, it constitutes actions of practices capable of reducing morbidity and mortality induced by pharmacotherapy. On the other hand, pharmaceutical services may face several barriers related to the implementation of these practices. These difficulties are associated with management, availability of an appropriate physical environment, integration with the multidisciplinary team, and acceptance of pharmaceutical interventions by health professionals. Objectives: This study aims to map and summarize the scientific evidence on the experiences and strategies used to implement pharmaceutical services in hospital geriatric units. Methods: The scoping review will be based on three electronic databases (PubMed, EMBASE, and Web of Science). Studies that met the inclusion criteria and are published by December 2022 will be selected. The screening, eligibility, extraction, and assessment of studies will be carried out by two independent researchers. Experimental and observational studies will be eligible for inclusion. Discussion: The experiences of incorporating pharmaceutical care into geriatric hospital units need to be better disseminated. Our review could support the performance of pharmaceutical care in other geriatric wards and has the potential to be a reference for multidisciplinary training. In addition, the study is related to the global challenge of the World Alliance for Patient Safety as it is a survey that will demonstrate strategies for safety in the use of medicines.

Contribution of Pharmaceutical Care to Person-centered Health Care and the Safety of Pharmacotherapy for Hospitalized Older Individuals in Brazil: An Investigative Single-arm Intervention Trial.

BACKGROUND: Adverse drug events (ADE) and medication errors (ME) provide large numbers of victims. Older people are more susceptible to these events, due to the continuing search for several chronic degenerative disease treatments. The Third Global Patient Safety Challenge announced the objective of reducing unnecessary polypharmacy, encouraging deprescription, and aiming to ensure the prescription of medications in an appropriate manner, based on the best evidence and taking into account the individual factors of people. OBJECTIVE: To evaluate whether Pharmaceutical Care (PC), when inserted in a geriatric ward and the context of person-centered health care, cooperates with the safety of pharmacotherapy in older individuals in Brazil. METHODS: This is an investigative, single-arm, preliminary study. INCLUSION CRITERIA: individuals aged ≥60 years and admitted to the geriatric ward between August 2019 to January 2020. The PC (with the practice of pharmacotherapeutic follow-up, medication reconciliation, and pharmacotherapy review) was made available to identify ADE and ME, as well as the associated factors and clinical outcomes, were analyzed. RESULTS: 60 participants were included. It was found that, on hospital admission, 93.3% of them were polymedicated and 86.7% had a history of using potentially inappropriate medications (PIM). ADE and ME were detected in 43 individuals (71.7%) and, in total, 115 incidents were identified, with drugs that act on the nervous system associated with them (31.9%). Acceptance of the PC's recommendations reached the rate of 85.2%. Polypharmacy (p=0.03) and the presence of multiple diseases (p=0.03) had an effect on the presentation of ADE and ME. The number of medications in use decreased in the comparison between admission and hospital discharge (p<0.0001). CONCLUSION: This investigative study indicated that ADE and ME are linked to the polypharmacy in use at the beginning of hospitalization. On the other hand, we showed that the PC (inserted in the multidisciplinary team) contributed to the deprescribing of medications at hospital discharge. Therefore, the PC can provide improvements in this scenario.

Effects of different moist orange pulp inclusions in the corn grain rehydration for silage production on chemical composition, fermentation, aerobic stability, microbiological profile, and losses.

This study evaluated the effects of different moist orange pulp (MOP) inclusions in corn grain rehydration for silage production as a strategy to store and use MOP and whether these inclusions result in adequate fermentation and aerobic stability (AE) and acceptable losses. Ground corn grain and MOP were weighed separately and mixed to obtain MOP inclusions of 21%, 34%, or 42%. The control treatment was obtained with corn rehydrated with distilled water and MOP inclusion of 0%, with five laboratory silos (15-L buckets) per treatment. Acid detergent fiber, acid detergent insoluble protein, acid detergent lignin, lactic acid, acetic acid, and ethanol contents increased linearly with increasing MOP inclusion, whereas starch, in vitro dry matter (DM) digestibility and butyric acid contents and pH decreased linearly. NH3 -N/TN content reduced quadratically and was minimal with 8.34 g/kg DM at 14% MOP inclusion. Total DM losses increased quadratically with maximal losses of 4.26% DM at 25% MOP inclusion. AE reduced by 2.8 h for each 1% increase in MOP inclusion. Rehydration of corn grain with MOP results in an adequate fermentation process. The inclusion of 34% MOP was the best because DM losses were lower and AE was not drastically reduced.

Efficacy and safety of repellents marketed in Brazil against bites from Aedes aegypti and Aedes albopictus: A systematic review.

BACKGROUND: Dengue, Zika and Chikungunya viruses represent a serious public health problem. No evidence is available on the efficacy of repellents commercially available in Brazil. This systematic review assessed the efficacy and safety of products containing repellents commercially available in Brazil for protection against bites from Aedes aegypti and Aedes albopictus. METHODS: We performed a systematic review using the CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science, AMED, LILACS and Scopus databases. Randomized clinical trials and non-randomized clinical trials comparing topical repellent products registered with the Brazilian Health Surveillance Agency were included. Main outcomes of interest investigated were adverse effects, percentage repellency and protection time against bites. Pairs of reviewers selected the studies, extracted the data and evaluated the risk of bias. RESULTS: Sixteen studies were included. No adverse effects were reported by the studies. Against Ae. aegypti: protection time using DEET (10% and 20%-spray) was similar to IR3535 (10% and 20%-spray) and longer than citronella (5%-spray). DEET (25%-solution) had longer protection time than eucalyptus (25%-solution), while DEET (20%-lotion) had longer protection time than citronella (10%-lotion). There was no difference in protection time between herbal repellents. DEET (7% and 15%- spray) had higher percentage repellency compared to both icaridin (7%-spray) and IR3535 (20%-spray). Against Ae. albopictus: DEET (15%-spray) had a similar protection time to icaridin (20%-spray), but longer than citronella (10%-spray). CONCLUSION: DEET proved more effective than the other synthetic and natural repellents marketed in Brazil for protecting against bites from the mosquito species investigated. All repellents studied exhibited satisfactory safety profile.

Comparison between hydroxyapatite/soapstone and hydroxyapatite/reduced graphene oxide composite coatings: Synthesis and property improvement.

Economic viability and eco-friendliness are important characteristics that make implants available to the population in a sustainable way. In this work, we evaluate the performance of a low-cost, widely available, and eco-friendly material (talc from soapstone) relative to reduced graphene oxide as reinforcement to brittle hydroxyapatite coatings. We employ a low-cost and straightforward technique, electrodeposition, to deposit the composite coatings on the titanium substrate. Corrosion, wear, and biocompatibility tests indicate that the reduced graphene oxide can be effectively replaced by talc without reducing the mechanical, anticorrosion, and biocompatible composite coatings properties. Our results indicate that talc from soapstone is a promising material for biomedical applications.

Crystal reorientation and plastic deformation of single-layer MoS2 and MoSe2 under uniaxial stress.

We investigate theoretically, through of first-principles calculations, the effect of the application of large in-plane uniaxial stress on single-layer of MoS2, MoSe2, and MoSSe alloys. For stress applied along the zigzag (zz) direction, we predict an anomalous behavior near the point fracture. This behavior is characterized by the reorientation of the MoS2 structure along the applied stress from zz to armchair due to the formation of transient square-lattice regions in the crystal, with an apparent crystal rotation of 30 degrees. After reorientation, a large plastic deformation [Formula: see text] remains after the stress is removed. This behavior is also observed in MoSe2 and in MoSSe alloys. This phenomenon is observed both in stress-constrained geometry optimizations and in ab initio molecular dynamics simulations at finite temperature and applied stress.

Crystal reorientation and plastic deformation of single-layer MoS2and MoSe2under uniaxial stress.

We investigate theoretically, through of first-principles calculations, the effect of the application of large in-plane uniaxial stress on single-layer of MoS2, MoSe2, and MoSSe alloys. For stress applied along the zigzag direction, we predict an anomalous behavior near the point fracture. This behavior is characterized by the reorientation of the MoS2structure along the applied stress from zigzag to armchair due to the formation of transient square-lattice regions in the crystal, with an apparent (although not real) crystal rotation of 30 degrees. After reorientation, a large plastic deformation √3-1 remains after the stress is removed. This behavior is also observed in MoSe2and in MoSSe alloys. This phenomenon is observed both in stress-constrained geometry optimizations and in ab initio molecular dynamics simulations at finite temperature and applied stress.

Nanomechanics of few-layer materials: do individual layers slide upon folding?

Folds naturally appear on nanometrically thin materials, also called "2D materials", after exfoliation, eventually creating folded edges across the resulting flakes. We investigate the adhesion and flexural properties of single-layered and multilayered 2D materials upon folding in the present work. This is accomplished by measuring and modeling mechanical properties of folded edges, which allows for the experimental determination of the bending stiffness (κ) of multilayered 2D materials as a function of the number of layers (n). In the case of talc, we obtain κ ∝ n 3 for n ≥ 5, indicating no interlayer sliding upon folding, at least in this thickness range. In contrast, tip-enhanced Raman spectroscopy measurements on edges in folded graphene flakes, 14 layers thick, show no significant strain. This indicates that layers in graphene flakes, up to 5 nm thick, can still slip to relieve stress, showing the richness of the effect in 2D systems. The obtained interlayer adhesion energy for graphene (0.25 N/m) and talc (0.62 N/m) is in good agreement with recent experimental results and theoretical predictions. The obtained value for the adhesion energy of graphene on a silicon substrate is also in agreement with previous results.

Water diffusion in carbon nanotubes: Interplay between confinement, surface deformation, and temperature.

In this article, we investigate, through molecular dynamics simulations, the diffusion behavior of the TIP4P/2005 water confined in pristine and deformed carbon nanotubes (armchair and zigzag). To analyze different diffusive mechanisms, the water temperature was varied as 210 ≤ T ≤ 380 K. The results of our simulations reveal that water presents a non-Arrhenius to Arrhenius diffusion crossover. The confinement shifts the diffusion transition to higher temperatures when compared with the bulk system. In addition, for narrower nanotubes, water diffuses in a single line, which leads to its mobility independent of the activation energy.

Water diffusion in rough carbon nanotubes.

We use molecular dynamics simulations to study the diffusion of water inside deformed carbon nanotubes with different degrees of deformation at 300 K. We found that the number of hydrogen bonds that water forms depends on nanotube topology, leading to enhancement or suppression of water diffusion. The simulation results reveal that more realistic nanotubes should be considered to understand the confined water diffusion behavior, at least for the narrowest nanotubes, when the interaction between water molecules and carbon atoms is relevant.

Synthesis and characterization of TPP/chitosan nanoparticles: Colloidal mechanism of reaction and antifungal effect on C. albicans biofilm formation.

In the present study chitosan (Chit) nanoparticles were synthetized by the ionic gelation process, using tripolyphosphate (TPP) as crosslinking agent. The TPP/Chit nanoparticle formation was evaluated by titrations, measuring electrical conductivity (k), zeta potential (ZP), hydrodynamic diameter (Dh), viscosity (η) and heat by isothermal calorimetry (ITC). The antifungal effects were evaluated by C. albicans time-kill assays, inhibition of C. albicans initial adhesion and biofilm formation in comparison with nystatin and chitosan. Conductometric titration exhibited a typical precipitation profile, with an inflection at molar ratio of [TPP]/[Chitmon] ≈ 0.3, suggesting a 1:3.3 stoichiometry. The highest Dh, ZP and η values were shown at the beginning of titrations, due to the intramolecular repulsion between Chit-Chit. With addition of TPP, the values showed gradual reduction, with an intermediary transition at [TPP]/[Chitmon] ≈ 0.16, which was attributed to the partial breakdown of interchain crosslinking and formation of discrete charged aggregates. After this point, reaction should occur by neutralization of these assemblies, causing new reduction in values of Dh, ZP and η until [TPP]/[Chitmon] ≈ 0.3, when they reached their lowest values. ITC experiment also showed the occurrence of two bindings (K1 = 3.6 × 103 and K2 = 7.7 × 104), which were entropy driven. Biological results showed lower C. albicans viability for TPP/Chit over 24 h compared with chitosan and nystatin at MIC and 2 MIC. Moreover, TPP/Chit showed 25-50% inhibition of C. albicans adhesion and biofilm formation. The results showed that TPP/Chit nanoparticles reduced the initial adhesion and biofilm formation of C. albicans and demonstrated potential for use in a formulation for the treatment of oral candidiasis.

Compression-Induced Modification of Boron Nitride Layers: A Conductive Two-Dimensional BN Compound.

The ability to create materials with improved properties upon transformation processes applied to conventional materials is the keystone of materials science. Here, hexagonal boron nitride (h-BN), a large-band-gap insulator, is transformed into a conductive two-dimensional (2D) material- bonitrol-that is stable at ambient conditions. The process, which requires compression of at least two h-BN layers and hydroxyl ions, is characterized via scanning probe microscopy experiments and ab initio calculations. This material and its creation mechanism represent an additional strategy for the transformation of known 2D materials into artificial advanced materials with exceptional properties.