Results of a brief online group application of the unified protocol for the prevention of emotional disorders in university students: a pilot study with multiple baseline experimental design / Resultados de una aplicación grupal breve en línea del protocolo unificado para la prevención de trastornos emocionales en estudiantes universitarios: un estudio piloto con diseño experimental de línea base múltiple

Los trastornos emocionales (TEs) son los trastornos más comunes entre la población joven. El desarrollo de programas preventivos de los TEs es fundamental para evitar su posible aparición. Los programas de prevención transdiagnósticos podrían presentar una ventaja sobre los existentes para mejorar las estrategias de regulación emocional. Así, el objetivo de este estudio ha sido determinar la viabilidad y eficacia preliminar de un programa breve basado en el Protocolo Unificado (PU). El proyecto consistió en un estudio piloto utilizando un diseño experimental de línea base múltiple. Nueve estudiantes universitarios recibieron un programa de 5 sesiones basado en el PU en formato grupal online. Se encontraron diferencias significativas después de la intervención en la regulación de las emociones, el apoyo social percibido y la evitación, con tamaños del efecto moderados-grandes (r de Cohen = .49 - .59). Estas mejoras mostraron aumentos en los seguimientos al mes y a los 3 meses. Esos resultados están en línea con los que muestran que los programas preventivos transdiagnósticos breves podrían ser útiles para la prevención de los TEs en población universitaria.(AU)

Emotional disorders (EDs) are the most common disorders among the young population. The development of preventive programs for EDs is essential to avoid their possible appearance. Transdiagnostic prevention programs could present an advantage over existing ones to im-prove emotional regulation strategies. Thus, the objective of this study has been to determine the preliminary feasibility and effectiveness of a brief program based on the Unified Protocol (UP). The project consisted of a pilot study using a multiple baseline experimental design. Nine university students received a 5-session program based on the UP in online-group format. Significant differences were found after the intervention for emo-tion regulation, perceived social support and avoidance, with moderate-large effect sizes (Cohen's r= .49-.59). These improvements showed in-creases at 1-month and 3-month follow-ups. Those results are in line with those showing that brief transdiagnostic preventive programs could be use-ful for the prevention of EDs in the university population.(AU)

PERIOPERATIVE CARE IN DIGESTIVE SURGERY: THE ERAS AND ACERTO PROTOCOLS - BRAZILIAN COLLEGE OF DIGESTIVE SURGERY POSITION PAPER.

BACKGROUND: The concept introduced by protocols of enhanced recovery after surgery modifies perioperative traditional care in digestive surgery. The integration of these modern recommendations components during the perioperative period is of great importance to ensure fewer postoperative complications, reduced length of hospital stay, and decreased surgical costs. AIMS: To emphasize the most important points of a multimodal perioperative care protocol. METHODS: Careful analysis of each recommendation of both ERAS and ACERTO protocols, justifying their inclusion in the multimodal care recommended for digestive surgery patients. RESULTS: Enhanced recovery programs (ERPs) such as ERAS and ACERTO protocols are a cornerstone in modern perioperative care. Nutritional therapy is fundamental in digestive surgery, and thus, both preoperative and postoperative nutrition care are key to ensuring fewer postoperative complications and reducing the length of hospital stay. The concept of prehabilitation is another key element in ERPs. The handling of crystalloid fluids in a perfect balance is vital. Fluid overload can delay the recovery of patients and increase postoperative complications. Abbreviation of preoperative fasting for two hours before anesthesia is now accepted by various guidelines of both surgical and anesthesiology societies. Combined with early postoperative refeeding, these prescriptions are not only safe but can also enhance the recovery of patients undergoing digestive procedures. CONCLUSIONS: This position paper from the Brazilian College of Digestive Surgery strongly emphasizes that the implementation of ERPs in digestive surgery represents a paradigm shift in perioperative care, transcending traditional practices and embracing an intelligent approach to patient well-being.

Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis.

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

Nurse-Initiated Protocol to Improve Timely Antibiotic Administration in Pediatric Open Fractures.

BACKGROUND: Early administration of antibiotics in the presence of open fractures is critical in reducing infections and later complications. Current guidelines recommend administering antibiotics within 60 min of patient arrival to the emergency department, yet trauma centers often struggle to meet this metric. OBJECTIVES: This study aims to evaluate the impact of a nurse-initiated evidence-based treatment protocol on the timeliness of antibiotic administration in pediatric patients with open fractures. METHODS: A retrospective pre-post study of patients who met the National Trauma Data Standard registry inclusion criteria for open fractures of long bones, amputations, or lawn mower injuries was performed at a Midwestern United States Level II pediatric trauma center. The time of patient arrival and time of antibiotic administration from preimplementation (2015-2020) to postimplementation (2021-2022) of the protocol were compared. Patients transferred in who received antibiotics at an outside facility were excluded. RESULTS: A total of N = 73 participants met the study inclusion criteria, of which n = 41 were in the preimplementation group and n = 32 were in the postimplementation group. Patients receiving antibiotics within 60 min of arrival increased from n = 24/41 (58.5%) preimplementation to n = 26/32 (84.4%) postimplementation (p< .05). CONCLUSIONS: Our study demonstrates that initiating evidence-based treatment orders from triage helped decrease the time from arrival to time of antibiotic administration in patients with open fractures. We sustained improvement for 24 months after the implementation of our intervention.

Use of Fever Duration to Guide Management of Urinary Tract Infection.

BACKGROUND: The appropriate duration of antimicrobial therapy for febrile urinary tract infection (fUTI) in children has not been established. This study examined the optimal duration of treatment for fUTI in children. METHODS: We created a protocol that used fever duration to determine the duration of antibiotic administration. Transvenous antibiotics were administered until 3 days after resolution of fever, followed by oral antibiotics for 1 week. Diagnosis of fUTI was based on a fever of 37.5°C or higher and a quantitative culture of catheterized urine yielded a bacteria count of ≥5 × 104. Acute focal bacterial nephritis (AFBN) and pyelonephritis (PN) were diagnosed on the basis of contrast-enhanced computed tomography (eCT) findings. We retrospectively reviewed treatment outcomes. RESULTS: Of the 78 patients treated according to our protocol, data from 58 were analyzed-49 children (30 boys) had PN and nine (three boys) had AFBN. Blood test results showed that patients with AFBN had significantly higher white blood cell counts and C-reactive protein levels than did those with PN; however, urinary findings and causative bacteria did not differ between groups. Time to resolution of fever and duration of intravenous antibiotic administration were significantly longer in patients with AFBN than in those with PN. However, average duration of AFBN treatment was 14.2 days, which was shorter than the previously reported administration period of 3 weeks. No recurrence was observed in AFBN patients. CONCLUSIONS: A protocol that used fever duration to determine the duration of antimicrobial treatment was useful. Invasive examinations, such as eCT, were not required.

Restrictive calcium replacement in septic shock: a multicenter before-after intervention study. / Reposición restrictiva de calcio en pacientes con shock séptico: estudio de intervención antes-después.

OBJECTIVES: To study the impact of a restrictive calcium replacement protocol in comparison with a liberal one in patients with septic shock. MATERIAL AND METHODS: Multicenter retrospective before-after study that estimated the impact of implementing a restrictive calcium replacement protocol in patients with septic shock. Patients admitted to an intensive care unit between May 2019 and April 2021 were assigned to liberal calcium replacement, and those admitted between May 2021 and April 2022 were assigned to a restrictive protocol. The primary outcome measure was 28-day mortality. Patients were matched with propensity scores. RESULTS: A total of 644 patients were included; liberal replacement was used in 453 patients and the restrictive replacement in 191. We paired 553 patients according to propensity scores, 386 in the liberal group and 167 in the restrictive group. Mortality did not differ significantly between the groups at 28 days (35.3% vs 32.3%, respectively; hazard ratio, 0.97; 95% CI, 0.72-1.29) or after resolution of septic shock (81.5% vs 83.8%; hazard ratio, 0.89; 95% CI, 0.73-1.09). Nor did scores on the Sepsis-related Organ Failure Assessment scale differ (2.1 vs 2.6; P = 0.20). CONCLUSION: The implementation of a restrictive calcium replacement protocol in patients with septic shock was not associated with a decrease in 28-day mortality in comparison with use of a liberal protocol. However, we were able to reduce calcium replacement without adverse effects.

OBJETIVO: Investigar el efecto de un protocolo de reposición restrictiva de calcio frente a una estrategia liberal en pacientes con shock séptico. METODO: Estudio multicéntrico, antes-después y retrospectivo que evaluó el efecto de la implementación de un protocolo de reposición restrictiva de calcio en pacientes con shock séptico. Los pacientes que ingresaron en unidades de cuidados intensivos (UCI) entre mayo de 2019 y abril de 2021 se asignaron al grupo con administración liberal, y los que se presentaron entre mayo de 2021 y abril de 2022 ­tras la implementación del protocolo­ al grupo con administración restrictiva. La variable de resultado principal fue la mortalidad a 28 días. Se realizó un emparejamiento por puntuación de propensión. RESULTADOS: Se incluyeron 644 pacientes, 453 en el grupo liberal y 191 en el grupo restrictivo. De los que 553 se emparejaron (386 en el grupo liberal, y 167 en el grupo restrictivo). No hubo diferencias entre los dos grupos en la mortalidad a los 28 días (35,3% vs 32,3%; HR: 0,97; IC 95%: 0,72-1,29), en la finalización del shock (81,5% vs a 83,8%; HR: 0,89; IC 95%: 0,73-1,09) ni en la puntuación de la escala SOFA (2,1 vs 2,6; p = 0,20). CONCLUSIONES: La implementación de un protocolo de administración restrictiva de calcio, en pacientes con shock séptico, no se asoció a una disminución de la mortalidad a los 28 días en comparación con una administración liberal. No obstante, la reposición de calcio podría reducirse sin efectos adversos.

Nursing care protocol for critical users with tracheostomy under mechanical ventilation.

OBJECTIVES: to develop and assess a nursing care protocol for critically ill users with tracheostomy under mechanical ventilation. METHODS: a methodological study, developed through two phases, guided by the 5W2H management tool: I) target audience characterization and II) technology development. RESULTS: thirty-four nursing professionals participated in this study, who presented educational demands in relation to care for critical users with tracheostomy, with an emphasis on standardizing care through a protocol and carrying out continuing education. FINAL CONSIDERATIONS: the creation and validity of new technologies aimed at this purpose enhanced the participation of nursing professionals and their empowerment in the health institution's microsectoral actions and in macrosectoral actions, highlighting the need for public policies that guarantee the conduct of a line of care for users with tracheostomy.

Increasing the Volume of Delivered Enteral Feeds Using a Volume-Based Feeding Protocol in a Neuroscience Intensive Care Unit.

BACKGROUND: Iatrogenic malnutrition is a significant burden to patients, clinicians, and health care systems. Compared with well-nourished patients, underfed patients (those who receive less than 80% of their daily energy requirement) have more adverse outcomes related to nutritional status. Volume-based protocols allow for catch-up titrations, are consistently superior to rate-based protocols, and can be implemented in most settings. LOCAL PROBLEM: This project was conducted in an 8-bed neuroscience intensive care unit in which up to 41% of patients who required enteral feeding were underfed. METHODS: This quality improvement clinical practice change project used a before-and-after design to evaluate (1) the effect of implementing a volume-based feeding protocol on the delivery of enteral feeds and (2) the effect of a nutrition-based project on staff members' attitudes regarding nutrition in critical care. The effectiveness of a volume-based feeding titration protocol was compared with that of a rate-based feeding protocol for achieving delivery of at least 80% of prescribed nutrition per 24-hour period. Staff members' attitudes were assessed using a survey before and after the project. RESULTS: During 241 enteral feeding days (n = 40 patients), the percentage of delivered enteral feeding volume and the percentage of days patients received at least 80% of the prescribed volume increased after volume-based feeding was implemented. After project implementation, 74 staff members reported increased emphasis on nutrition delivery in their practice and a higher level of agreement that nutrition is a priority when caring for critically ill patients. CONCLUSIONS: Using a volume-based feeding protocol with supplemental staff education resulted in improved delivery of prescribed enteral feeding.

Implementing a Preoperative Anemia Optimization Protocol for Cardiovascular Surgery Patients: A Quality Improvement Project.

BACKGROUND: Patients with anemia have poorer outcomes following cardiac surgery than do those without anemia. To improve outcomes, the Enhanced Recovery After Surgery cardiac recommendations include optimizing patients' condition, including treating anemia, before surgery. LOCAL PROBLEM: Despite implementing Enhanced Recovery After Surgery initiatives, a midwestern cardiothoracic surgery group recognized a care gap in preoperative patients with anemia. No standardized protocol was in use. METHODS: An anemia optimization protocol was developed for perioperative care of patients with anemia. Data from retrospective medical record review were analyzed to determine relationships between protocol use and secondary outcomes. The protocol was created using best evidence and expert consensus. Cardiac surgery and hematology specialists revised the protocol and agreed on a final version. The protocol was integrated into the consultation process for cardiac surgery patients. RESULTS: During the implementation period, 23 of 55 patients with anemia (42%) received interventions via the anemia optimization protocol. The mean quantity of packed red blood cells transfused perioperatively per patient was 1.9 U in the protocol group and 3.5 U in the nonprotocol group. In the subgroup of patients experiencing postoperative acute kidney injury, the mean increase in creatinine level was 0.65 mg/dL in the protocol group and 1.52 mg/dL in the nonprotocol group. Four patients in the protocol group (17%) and 6 patients in the nonprotocol group (19%) experienced postoperative acute kidney injury. CONCLUSION: Preoperative anemia is associated with poorer cardiac surgical outcomes. Incorporating the anemia optimization protocol into practice may mitigate the risk of postoperative complications for patients with anemia. Continued use of the protocol is recommended.

Implementing protocol-based relaparoscopy for severe complications in laparoscopic colorectal surgery.

BACKGROUND: Although laparoscopy has demonstrated growing applications for either primary colorectal resections or reoperations, no standardized criteria for implementing laparoscopy in revisional surgery have been reported. This study analyzes a single-center series of major complications after laparoscopic colorectal surgery, undergoing laparoscopic (LR), or open reoperations in compliance with a hemodynamics-based institutional management. METHODS: This study retrospectively analyzes a series of consecutive patients who primarily underwent either laparoscopic left colectomy or low anterior resection in a tertiary referral center between 2016 and 2021. Major complications requiring reoperation (MCR) were managed through an interdisciplinary protocol and submitted to reoperation according to patient hemodynamics and intra-abdominal contamination. A cohort analysis primarily assessed treatment failure rates (i.e., 90-day mortality and need for further surgery), while postoperative morbidity was secondarily examined. RESULTS: Out of 1137 laparoscopic colorectal resections, 497 patients met eligibility criteria, while 45 (9.1%) developed MCRs were managed according to the standardized interdisciplinary protocol. Revisional surgery was performed through either LR (66.7%) or (33.3%). Treatment failure was 13.3% overall, including additional surgery (11.1%) and 90-day mortality (6.6%) after reoperation. In both overall and anastomotic leak-specific MCRs, relaparoscopy resulted in minimized length of hospital stay, postoperative morbidity, and intensity of care. CONCLUSIONS: Relaparoscopy for MCR preserves clinical benefits related to minimally invasive colorectal surgery. Further studies should investigate applicative determinants and impediments related to the center volume.

Counseling Protocol for a Transitional Intervention for Debilitating Hyperacusis.

INTRODUCTION: This clinical focus article describes a structured counseling protocol for use with protected sound management and therapeutic sound in a transitional intervention for debilitating hyperacusis. The counseling protocol and its associated visual aids are crafted as a teaching tool to educate affected individuals about hyperacusis and encourage their acceptance of a transitional intervention. DESCRIPTION OF COUNSELING COMPONENTS: The counseling protocol includes five components. First, the patient's audiometric results are reviewed with the patient, and the transitional intervention is introduced. An overview of peripheral auditory structures and central neural pathways and the concept of central gain are covered in the second and third components. Maladaptive hyper-gain processes within the auditory neural pathways, which underlie the hyperacusis condition, and associated connections with nonauditory processes responsible for negative reactions to hyperacusis are covered in the fourth component. Detrimental effects from misused hearing protection devices (HPDs) and the necessity to wean the patient from overuse of HPDs are also discussed. In the fifth component, the importance of therapeutic sound is introduced as a tool to downregulate hyper-gain activity within the auditory pathways; its implementation in uncontrolled and controlled sound environments is described. It is explained that, over the course of the transitional intervention, recalibration of the hyper-gain processes will be ongoing, leading to restoration of normal homeostasis within the auditory pathways. In turn, associated activation of reactive nonauditory processes, which contribute to hyperacusis-related distress, will be reduced or eliminated. As recalibration progresses, there will be less need for protected sound management and sound therapy. Sound tolerance will improve, hyperacusis will subside, and daily activities in typical healthy sound environments will again become routine. RESULTS AND CONCLUSION: The combination of counseling with protected sound management and therapeutic sound is highlighted in companion reports, including a summary of the outcomes of a successful trial of the transitional intervention.

The impact of Covid-19 pandemic on the research portfolio and approval turnaround time at the Kenya Medical Research Institute.

BACKGROUND: The Covid-19 pandemic led to an unprecedented impact on many sectors globally including research. We assessed the impact of the Covid-19 pandemic on the research portfolio, and on the approval turnaround time for research protocols submitted to the Scientific and Ethics Review Unit (SERU), at the Kenya Medical Research Institute (KEMRI). METHODS: We compared research protocols submitted between October 01, 2019 and March 31, 2020 (Period 1), to those submitted between April 1 and September 30, 2020 (Period 2). A document review tool was used to extract data from the 198 research protocols reviewed and approved over the two periods. RESULTS: In the two periods under review, the single largest percentage of protocols (89/198, 45.4%) involved infectious and parasitic diseases, and the single largest percentage of study designs was cross-sectional (75/198, 38%). Before the pandemic, the median time taken to review KEMRI-linked protocols was 87 days and for non-KEMRI linked protocols it was 121 days. During the pandemic, approval turnaround time dropped for both KEMRI and non-KEMRI protocols to 66 days and 92 days, respectively, due to the streamlined processes at the KEMRI SERU. CONCLUSION: The research portfolio was minimally affected by the pandemic. The adoption of email submission, and faster-than-usual processing and review protocols during the pandemic reduced the approval turnaround time.

The implementation of an inflammatory bowel disease-specific enhanced recovery after surgery protocol: an observational cohort study.

BACKGROUND: The implementation of Enhanced Recovery After Surgery (ERAS) protocols has resulted in improved postoperative outcomes in colorectal cancer surgery. The evidence regarding feasibility and impact on outcomes in surgery for inflammatory bowel disease (IBD) is limited. METHODS: We performed a retrospective observational cohort study, comparing patient trajectories before and after implementing an IBD-specific ERAS protocol at Zealand University Hospital. We assessed the occurrence of serious postoperative complications of Clavien-Dindo grade 3 or higher as our primary outcome, with postoperative length of stay in days and rate of readmissions as secondary outcomes, using χ2, Mann-Whitney test, and odds ratios adjusted for sex and age. RESULTS: From 2017 to 2023, 394 patients were operated on for IBD and included in our study. In the ERAS cohort, 39/250 patients experienced a postoperative complication of Clavien-Dindo grade 3 or higher compared to 27/144 patients in the non-ERAS cohort (15.6% vs. 18.8%, p = 0.420) with an adjusted odds ratio of 0.73 (95% CI 0.42-1.28). There was a significantly shorter postoperative length of stay (median 4 vs. 6 days, p < 0.001) in the ERAS cohort compared to the non-ERAS cohort. Readmission rates remained similar (22.4% vs. 16.0%, p = 0.125). CONCLUSIONS: ERAS in IBD surgery was associated with faster patient recovery, but without an impact on the occurrence of serious postoperative complications and rate of readmissions.

Outcomes of a same day discharge protocol in patients undergoing mastectomy and implant reconstruction.

BACKGROUND: Finite hospital resources has required a closer look at resource allocation. This has prompted a shift toward same day surgeries and a focus on reducing hospital readmissions. Following the institution of a same day discharge protocol for mastectomy and mastectomy with immediate reconstruction, we sought to assess differences in the length of stay and readmission rates. METHODS: This retrospective review evaluates all cases of mastectomy with or without immediate reconstruction performed at a single high-volume center between June 2019 and March 2021. Average length of stay, 30-day readmission rates, Anesthesia Society Assessment class, and type of immediate reconstruction were assessed. Autologous reconstructions were excluded. RESULTS: A total of 413 patients underwent mastectomy with or without reconstruction (n = 148 pre protocol and n = 265 during protocol) between June 2019 and March 2021. Of those 413 patients, 180 underwent reconstruction (n = 62 pre protocol and n = 118 during protocol). The average length of stay after mastectomy following the implementation of the same day discharge protocol was decreased at 0.6 days (n = 265) compared to preimplementation at 1.02 days (n = 148), p < 0.001. The 30-day readmission rate was not significant between the groups, p = 0.13. A total of 180 patients underwent immediate reconstruction after mastectomy. The average length of stay after mastectomy with immediate reconstruction following implementation of the same day discharge protocol was shorter than preimplementation at 1.05 days preimplementation (n = 62) versus 0.58 days following implementation (n = 118), p < 0.001; this finding was significant for both prepectoral and subpectoral implants, p < 0.001. There was no significant difference in 30-day readmission rates between the groups with immediate reconstruction, p = 0.34. CONCLUSION: Same day discharge for mastectomy with reconstruction is as safe as the more widely recognized same day discharge practice for patients with mastectomy alone.

[Ethics of care: Assessment of the ethical issues in the protocols or consensuses on mechanical restraint in force in Spain]. / Ética de los cuidados: valoración de los contenidos éticos en los protocolos o consensos de contención mecánica vigentes en España.

INTRODUCTION: Mechanical restraints are widely used in health care practice, despite the numerous ethical conflicts they raise. The aim of this study is to evaluate the ethical considerations contemplated in the current protocols on mechanical restraint in Spain. METHOD: Systematic review in PubMed, WOS and Scopus, Google and Google Scholar. An ad hoc list of 30 items was used to evaluate the ethical content of the protocols. The quality of guidelines was assessed with AGREE II. RESULTS: The need for informed consent (IC) is reflected in 72% of the documents, the IC model sheet is included in only 41% of them, the rest of the analyzed characteristics on IC are fulfilled in percentages between 6% (the document includes the need to reevaluate the indication for IC) and 31% (the document contemplates to whom it should be requested). More than 20 ethical contents are reflected in 31% of them and less than 10 in 19% of the guidelines. The quality of the guides, according to AGREE II, ranged from 27 to 116 points (maximum possible 161), with a mean score of 68.7. Only 9% of the documents were classified as high quality. Finally, the correlation between ethical content and quality measured with AGREE II was 0.75. CONCLUSIONS: The variability of ethical contents in guidelines on mechanical restraints is very high. The ethical requirements to be included in protocols, consensus or Clinical Practice Guidelines should be defined.

Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid.

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.

A hospital management algorithm for acute poisoning by Paraquat® in a pediatric population, a series of cases / Algoritmo de manejo hospitalario para la intoxicación aguda por Paraquat® en población pediátrica, serie de casos.

Paraquat®, or N,N'-dimethyl-4,4'-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.

El dicloruro de 1,1'-dimetil-4,4'-bipiridilo (Paraquat®) es un compuesto químico de la familia de las piridinas, utilizado como herbicida no selectivo y desecante. Este compuesto puede causar intoxicación aguda por todas las vías de exposición. En el momento, no hay un antídoto conocido y los tratamientos disponibles, incluidos los pediátricos, se basan en contrarrestar su absorción y propiciar su remoción oportuna. Se describe una serie de casos de 14 pacientes pediátricos, procedentes en su mayoría del departamento del Cauca, con intoxicación aguda por ingestión de paraquat. Los pacientes fueron remitidos y atendidos en un hospital de mediana a alta complejidad en el suroccidente colombiano, con un protocolo institucional para el manejo de la intoxicación aguda por el herbicida. La intoxicación aguda con paraquat por vía oral se asocia con una alta tasa de mortalidad, aún con atención médica oportuna, pues fácilmente se alcanzan concentraciones sistémicas para ser fulminante. Basado en la literatura disponible, el Hospital Universitario San José ha propuesto un protocolo clínico ­adecuado para la intoxicación aguda por paraquat en población pediátrica­ que incluye manejo estándar temprano, tratamiento inmunosupresor y antioxidante, y técnicas para su remoción sistémica.