[Utility of the AGREE tool for the development and evaluation of clinical protocols: From theory to clinical practice]. / Utilidad del instrumento AGREE para la elaboración y la evaluación de protocolos clínicos: de la teoría a la práctica clínica.

INTRODUCTION AND OBJECTIVE: Clinical protocols are tools for the delivery of optimal and quality healthcare. However, there are often shortcomings in the quality of their design that invalidate their implementation. The aim of this study is to describe a systematic evaluation of clinical protocols, to analyse their quality in order to enable their implementation. MATERIALS AND METHODS: Descriptive study that included the clinical protocols assessed by the Committee of Reviewers of Clinical Practice Recommendations and Health Technologies of a tertiary hospital during 11years of its existence between 2013 and 2023. The AGREE instrument was used to assess the quality of the protocols received, calculating standardised scores by item and domain, and categorising them into: a)excellent (90-100%), b)good (70-89%), c)improvable (50-69%), d)very improvable (30-49%), e)deficient (10-29%), and f)very deficient: 0-9%. RESULTS: Of the 59 documents received by the Commission, 32 were subsidised for AGREE evaluation. The highest scoring domain was «Scope and objective¼, with excellent scores for 29 protocols; the remaining domains had scores ranging from 58.5%-100% for «Rigour in elaboration¼ and 0-100% for «Independence¼. By items, scores ranged from 85.7-100% for «Target users of the protocol are clearly defined¼ to 0-100% for the items «Potential costs of implementing recommendations¼ and «Conflict of interest¼. Of the 32 protocols, 9 were highly recommended, 22 were recommended with modifications/conditions and one was not recommended. CONCLUSIONS: The AGREE tool makes it possible to systematize both the drafting of clinical protocols by the authors and their evaluation by the Clinical Practice Recommendations and Health Technologies Review Committee. This makes it possible to have applicable and quality protocols in our hospital, which results in an improvement in the quality of healthcare.

Association between early manifestations of infection or sepsis and prognosis in a high complexity hospital in the city of Medellín.

OBJECTIVE: To identify the first symptoms and signs of patients with suspected infection or sepsis and their association with the composite outcome of admission to the Intensive Care Unit (ICU) or mortality. DESIGN: Prospective cohort study between June 2019 and March 2020. SETTING: Hospital Universitario San Vicente Fundación, Colombia. PATIENTS: Over 18 years of age with suspicion or confirmation of sepsis, which required hospitalization. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Symptoms and signs associated with infection, with their time of evolution, specified in the study. RESULTS: From 1005 eligible patients, 261 were included. After multivariable adjustment with a logistic regression model, the main factors for ICU admission or mortality were heart rate (OR 1.04 with 95% CI 1.04-3.7), respiratory rate (OR 1.19 with 95% CI 1.0-1.4) and capillary refill time (OR 3.4 with 95% CI 1.9-6.1). CONCLUSIONS: Heart rate, respiratory rate, and capillary refill may behave as early predictors of ICU admission and mortality in cases of sepsis.

Proton Shell Gaps in N=28 Nuclei from the First Complete Spectroscopy Study with FRIB Decay Station Initiator.

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

Indomethacin-omeprazole as therapeutic hybrids? Salt and co-amorphous systems enhancing physicochemical and pharmacological properties.

Multidrug therapeutic hybrids constitute a promising proposal to overcome problems associated with traditional formulations containing physical mixtures of drugs, potentially improving pharmacological and pharmaceutical performance. Indomethacin (IND) is a non-selective non-steroidal anti-inflammatory drug (NSAIDs) that acts by inhibiting normal processes of homeostasis, causing a series of side effects, such as gastrointestinal symptoms. Proton pump inhibitors, such as omeprazole (OME), have been used to treat such gastrointestinal tract symptoms. In this work, two new multidrug therapeutic hybrids were prepared (an IND:OME salt and an IND:OME co-amorphous system) by ball mill grinding crystalline IND and OME under different conditions, i.e., liquid assisted grinding (LAG) with ethanol and dry grinding, respectively. The crystalline salt returned to a neutral state co-amorphous system when submitted to ball mill grinding in the absence of solvent (dry grinding), but the reverse process (LAG of the IND:OME co-amorphous system) showed partial decomposition of OME. The IND:OME co-amorphous system showed a higher physical stability than the neat IND and OME amorphous materials (with an amorphous stability longer than 100 days, compared to 4 and 16 h for the neat amorphous drugs, respectively, when stored at dry conditions at room temperature). Furthermore, OME presented a higher chemical stability in solution when dissolved from a salt form than from the pure crystalline form. The dissolution studies showed a dissolution enhancement for IND in both salt (1.8-fold after 8 h of dissolution) and co-amorphous (2.5-fold after 8 h of dissolution) forms. Anti-inflammatory activity using a mice paw oedema model showed an increase of the pharmacological response to IND at a lower dose (∼5mg/kg) for both IND:OME salt (2.8-fold) and IND:OME co-amorphous system (3.2-fold) after 6 h, when compared to the positive control group (IND, administered at 10 mg/kg). Additionally, the anti-inflammatory activity of both salt and co-amorphous form was faster than for the crystalline IND. Finally, an indomethacin-induced gastric ulceration assay in mice resulted in a higher mucosal protection at the same dose (40 mg/kg) for both IND:OME salt and IND:OME co-amorphous system when compared with crystalline OME.

SKELETAL MUSCLE SENSITIVITY TO WASTING INDUCED BY UROTHELIAL CARCINOMA.

BACKGROUND: Skeletal muscle wasting is a common phenotypic feature of several types of cancer, and it is associated with functional impairment, respiratory complications, and fatigue. However, equivocal evidence remains regarding the impact of cancer-induced muscle wasting on the different fiber types. AIM: The aim of this study was to investigate the impact of urothelial carcinoma induced in mice on the histomorphometric features and collagen deposition in different skeletal muscles. MATERIALS AND METHODS: Thirteen ICR (CD1) male mice were randomly assigned into two groups: exposed to 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for 12 weeks, plus 8 weeks of tap water (BBN, n = 8) or with access to tap water for 20 weeks (CONT, n = 5). Tibialis anterior, soleus, and diaphragm muscles were collected from all animals. For cross-sectional area and myonuclear domain analysis, muscle sections were stained with hematoxylin and eosin, and for collagen deposition assessment, muscle sections were stained with picrosirius red. RESULTS: All animals from the BBN group developed urothelial preneoplastic and neoplastic lesions, and the tibialis anterior from these animals presented a reduced cross-sectional area (p < 0.001), with a decreased proportion of fibers with a higher cross-sectional area, increased collagen deposition (p = 0.017), and higher myonuclear domain (p = 0.031). BBN mice also showed a higher myonuclear domain in the diaphragm (p = 0.015). CONCLUSION: Urothelial carcinoma induced muscle wasting of the tibialis anterior, expressed by a decreased cross-sectional area, higher infiltration of fibrotic tissue, and increased myonuclear domain, which also increased in the diaphragm, suggesting that fast glycolytic muscle fibers are more susceptible to be affected by cancer development.

Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB.

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.

Prevalencia del Estrés Postraumático en médicos residentes, expuestos al SARS-COV-2 / Prevalence of posttraumatic stress in resident doctors, exposed to SARS-COV-2

Objetivo: Determinar la prevalencia del trastorno de estrés postraumático (TEPT) en una muestra de médicos residentes del Hospital de Clínicas, José de San Martín, Buenos Aires, Argentina, un año después del cierre total durante la cuarentena por COVID-19. Materiales y métodos: Se administraron los siguientes cuestionarios autoadministrados: una encuesta demográfica, el cuestionario de la Escala de Trauma de Davidson y la Escala de Experiencias Disociativas (EED). Se excluyeron a los residentes de primer año de especialidades básicas, a aquellos que por su especialidad no tienen contacto con pacientes y a los médicos con licencia fueron excluidos. Resultados: La prevalencia de TEPT fue de 24.3% (n=25). Las medianas de las puntuaciones de DES fueron mayores en los participantes con puntaje positivo para TEPT en comparación con los que no lo presentaban (Mann-Whitney U:13.30, p = 0.001). Se encontraron asociaciones entre el género (X2:6.074, p = 0.013), el TEPT y el tipo de especialidad (prueba exacta de Fisher, p = 0.017). No se encontraron otras asociaciones entre las demás variables analizadas y el TEPT. Conclusion: La prevalencia del TEPT fue similar a los informes previos. Se hallaron asociaciones entre este desorden, el género y el tipo de especialidad. Estos resultados deberían llamar la atención de los sistemas de salud para establecer medidas preventivas y terapéuticas para manejar esta situación.

Objective: Determine the prevalence of posttraumatic stress disorder (PTSD) in a sample of resident doctors of the Hospital de Clínicas, José de San Martín, Buenos Aires, Argentina, one year after the total closure during the quarantine by COVID-19. Materials and Methods: The following self-administered questionnaires were dispensed: a demographic survey, the Davidson Trauma Scale questionnaire, and the Scale of Dissociative Experiences (EED). First year residents of basic specialties were excluded, those who for their specialty do not have contact with patients and licensed doctors were excluded. Results: PTSD prevalence was 24.3% (n = 25). The medium-sized ones were greater in the participants with positive score for PTSD compared to those who did not present it (Mann-Whitney U: 13.30, p = 0.001). Associations between the genre were found (X2: 6,074, p = 0.013), the PTSD and the type of specialty (Fisher's exact test, p = 0.017). No other associations were found between the other variables analyzed and the PTSD. Conclusion: The prevalence of the PTSD was similar to the previous reports. Associations between this disorder, gender and type of specialty were found. These results should draw the attention of health systems to establish preventive and therapeutic measures to handle this situation