Effects of Exercise Intervention for the Management of Delirium in Hospitalized Older Adults: A Randomized Clinical Trial.

OBJECTIVE: Delirium is a serious neuropsychiatric syndrome frequently occurring in hospitalized older adults, for which pharmacological treatments have shown limited effectiveness. Multicomponent physical exercise programs have demonstrated functional benefits; however, the impact of exercise on the course of delirium remains unexplored. The aim of this study was to investigate the effect of an individualized, multicomponent exercise intervention on the evolution of delirium and patient outcomes. DESIGN: A single-center, single-blind randomized controlled trial. SETTING AND PARTICIPANTS: Medical inpatients with delirium in an acute geriatric unit of a tertiary public hospital. METHODS: Thirty-six patients (mean age 87 years) were recruited and randomized into 2 groups. The control group received usual care and the intervention group received individualized physical exercise (1 daily session) for 3 consecutive days. Primary endpoints were the duration and severity of delirium (4-AT, Memorial Delirium Assessment Scale) and change in functional status [Barthel Index, Short Physical Performance Battery, Hierarchical Assessment of Balance and Mobility (HABAM), and handgrip strength]. Secondary endpoints included length of stay, falls, and health outcomes at 1- and 3-month follow-up. RESULTS: The intervention group showed more functional improvement at discharge (HABAM, P = .015) and follow-up (Barthel, P = .041; Lawton P = .027). Less cognitive decline was observed at 1 and 3 months (Informant Questionnaire on Cognitive Decline in the Elderly, P = .017). Exercise seemed to reduce delirium duration by 1 day and contribute to delirium resolution at discharge, although findings did not reach statistical significance. No exercise-related adverse events occurred. CONCLUSION AND IMPLICATIONS: Findings suggest that individualized exercise in acutely hospitalized older patients with delirium is safe, may improve delirium course and help preserve post-hospitalization function and cognition.

Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients.

Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fracture patients, exploring the possibility of integrating objective methods into future predictive models of delirium. Sixty hip fracture patients were recruited. Blood and CSF samples were collected at the time of spinal anesthesia when none of the subjects had delirium. Patients were assessed daily using the 4AT scale, and based on these results, they were divided into POD and non-POD groups. The Olink® platform was used to analyze 45 cytokines. Twenty-one patients (35%) developed POD. In the subsample of 30 patients on whom proteomic analyses were performed, a proteomic profile was associated with the incidence of POD. Chemokine (C-X-C motif) ligand 9 (CXCL9) had the strongest correlation between serum and CSF samples in patients with POD (rho = 0.663; p < 0.05). Although several cytokines in serum and CSF were associated with POD after hip fracture surgery in older adults, there was a significant association with lower preoperative levels of CXCL9 in CSF and serum. Despite the small sample size, this study provides preliminary evidence of the potential role of molecular biomarkers in POD, which may provide a basis for the development of new delirium predictive models.

Sentinel Lymph Node Biopsy in Breast Cancer with 99mTc-Tilmanocept: A Multicenter Study on Real-Life Use of a Novel Tracer.

99mTc-tilmanocept is a novel radiopharmaceutical for sentinel lymph node (SLN) biopsy in breast cancer. Our aim was to describe results with 99mTc-tilmanocept in a heterogeneous group of breast cancer patients scheduled for SLN biopsy. Methods: Radiotracer preparation followed the manufacturer's indications. Local protocols for SLN detection within 9 participant centers were not changed for the entire duration of the study. In total, 344 patients with T1-T4, N0-N2 breast cancer (352 lesions) were included. Superficial (intradermal or periareolar) or deep (peritumoral or intratumoral) injections were performed. The doses were adjusted depending on the scheduled time for surgery. Results: Lymphoscintigraphy was able to depict at least 1 SLN in 339 of 352 breast lesions (96.3%), and the intraoperative SLN detection rate reached 97.2%. On univariable analysis, SLN detection rates did not differ by age, clinical T or N stage, tumor location, histologic subtype, or prior neoadjuvant therapy. Lymphoscintigraphy showed higher SLN detection in patients with a normal weight (body mass index < 25) than in those who were overweight or obese (body mass index ≥ 25), at 99.2% versus 94.6%, respectively (P = 0.031). The proportion of patients with preoperative lymphoscintigraphic detection or excised SLNs was higher with superficial than deep injections. Reinjected cases were significantly lower when superficial injection was chosen first (P < 0.001). Injection site and the tumor markers human epidermal growth factor receptor 2 and estrogen receptor had an impact on preoperative SLN visualization and intraoperative localization. In 80 cases, SLN biopsy resulted in a positive lymph node. During a mean follow-up of 19 mo, no axillary recurrences were observed. Conclusion: Whatever the protocol, 99mTc-tilmanocept showed good results in a heterogeneous breast cancer population, although the best results were achieved when a superficial injection was chosen.

Randomized Trial of Deep Vein Thrombosis Chemoprophylaxis with Bemiparin and Enoxaparin in Patients with Moderate to High Thrombogenic Risk Undergoing Plastic and Reconstructive Surgery Procedures.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication during postoperative convalescence characterized by hypercoagulability, vascular endothelium damage and blood stasis. It increases noticeably in peri/postoperative phases of surgery procedures. Pulmonary embolism secondary to iliofemoral DVT is a frequent cause of death. METHODS: Adult patients scheduled for plastic and reconstructive surgery (PRSx) with moderate to high thrombogenic risk were selected. We evaluated the efficacy and safety of bemiparin compared to enoxaparin as chemoprophylaxis for DVT. Following balanced general anesthesia techniques, patients were randomly assigned for subcutaneous enoxaparin 40 IU (Group-E) or bemiparin 3500 IU (Group-B) q24h starting 6 h after procedure conclusion for at least 10 days. All patients were evaluated for DVT through Doppler ultrasound mapping of the lower limbs. RESULTS: Seventy-eight patients were evaluated, mostly women (83%), physical status ASA II (59%), ASA III (10%); Caprini's thrombogenic risk score 3-4 (moderate) 58%, 5-6 (high) 29%, > 6 (too high) 13%; demographics, clinical variables and scores were similar between groups. Median drainage time in breast surgery was 4 days in both groups (p = 0.238). In the case of abdominal surgery, median was 14 days in Group-E versus 13 days in Group-B (p = 0.059). No DVT was detected in either group. CONCLUSIONS: DVT was prevented with bemiparin, without significant bleeding increase nor adverse events; moreover, the cost of bemiparin is lower than enoxaparin. Bemiparin can be considered as alternative drug for DVT chemoprophylaxis in PRSx procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Optimisation of a key cross-coupling reaction towards the synthesis of a promising antileishmanial compound.

During the course of a research program aimed at identifying novel antileishmanial compounds, a multi-gram synthesis of N-(trans-4-((4-methoxy-3-((R)-3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)cyclohexyl)-2-methylpropane-1-sulfonamide (( R )-1) was required. This letter describes optimisation of the reaction conditions and protecting group strategy for a key Buchwald-Hartwig coupling, delivering the required quantities of ( R )-1, as well as further compounds in the series.

Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis.

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (1) for VL.

Reducing by 50% the incidence of maternal hypotension during elective caesarean delivery under spinal anesthesia: Effect of prophylactic ondansetron and/or continuous infusion of phenylephrine - a double-blind, randomized, placebo controlled trial.

BACKGROUND: Prophylactic administrations of ondansetron or phenylephrine have been reported to provide a protective effect against hypotension in women undergoing cesarean delivery under spinal anesthesia (SA). The main hypothesis is that ondansetron improves the hemodynamic response, especially combined with phenylephrine infusion. METHODS: This prospective, double-blind, randomized, placebo-controlled study included 265 healthy pregnant women scheduled for elective cesarean delivery under SA. Women were randomly allocated into four groups to receive either placebo (control), ondansetron (O) 8 mg intravenously before induction of SA, phenylephrine infusion (50 mcg/min) (P) or ondansetron plus phenylephrine (OP). Demographic, obstetric, intraoperative timing, and anesthetic variables were assessed at 16 time points. Anesthetic variables assessed included blood pressure, heart rate, oxygen saturation, nausea, vomiting, electrocardiographic changes, skin flushing, discomfort or pruritus, and vasopressor requirements. RESULTS: There were differences (P = 0.0001) in the number of patients with hypotension (50.8% control, 44.6% O, 20.9% P, 25.0% OP), the percentage of time points (P = 0.0001) with systolic hypotension per patient (17.4% control, 8.7% O, 2.1% P, 6.7% OP) and the number of patients requiring supplementary boluses of ephedrine (P = 0.003), phenylephrine (P = 0.017) or atropine (P = 0.0001). CONCLUSIONS: A 50 µg/min phenylephrine infusion reduces by 50%, the incidence of maternal hypotension compared with placebo, but infusions of phenylephrine are still not routine in our environment. Prophylactic ondansetron 8 mg might be considered in this situation, because it does not reduce the incidence of maternal hypotension but diminishes its severity, reducing the number of hypotensive events per patient by 50%.

Hambre, miseria y enfermedad en latinoamérica y el caribe: el papel de la nutrición en las enfermedades tropicales desatendidas (ETDs) en nicaragua / Hunger, misery and disease in Latin America and the Caribbean: the role of nutrition in neglected tropical diseases (NTDs) in Nicaragua

La alimentación y la nutrición adecuadas son el primer y el más importante de los derechos humanos fundamentales y de los determinantes de la salud de las personas. Con el propósito de ayudar a reducir el impacto del hambre y facilitar el control y la eliminación de las enfermedades tropicales desatendidas (ETDs), contribuyendo al alcance de la seguridad alimentaria en la población escolar del Departamento de Chinandega (Nicaragua), se desarrolló el proyecto piloto “Hambre, miseria y enfermedad: el papel de la nutrición en las enfermedades tropicales desatendidas (ETDs) en Nicaragua”. El presente artículo documenta esta experiencia. Para conseguir los objetivos planteados se organizó una jornada científica con expertos en nutrición y en las ETDs, un panel elaboró las conclusiones que sirvieron para la redacción del documento de consenso, en el cual se fundamentó la elaboración de los materiales a ser utilizados en la intervención educativa: “Alimentación para crecer sano”, manual dirigido a los promotores de salud y “Manual de estrategias educativas: alimentación para crecer sano” dirigido a los escolares. Se realizaron cuatro jornadas de capacitación que inicialmente involucró a 80 maestros de 20 escuelas, y que en la última jornada logró sumar 145 docentes. Seguidamente se desarrolló la fase de multiplicación en las escuelas, con la participación de 2.327 niños de entre 7 y 14 años de edad. En esta experiencia la receptividad de los docentes, la mejora en sus habilidades y conocimientos son una garantía para la replicación en los niños y niñas(AU)

Food and proper nutrition are the first and most important of fundamental human rights and the determinants of health of people. In order to help reduce the impact of hunger and facilitate the control and elimination of neglected tropical diseases (NTDs), contributing to the extent of food safety in the school population of the Department of Chinandega (Nicaragua), the pilot project “Hunger, misery and disease: the role of nutrition in neglected tropical diseases (NTDs) in Nicaragua” was developed. This article documents this experience. To achieve the goals a scientific conference with experts in nutrition and NTDs was organized, a panel drew conclusions that were used for drafting the consensus document in which the development of the materials was based to be used in the intervention education: A “Food to grow healthy” manual aimed at health promoters and a “Manual of educational strategies: healthy food for growth” aimed at schoolchildren. Four days of training initially involved 80 teachers from 20 schools were made, and on the last day managed to reach 145 teachers. Then the multiplication phase in schools was developed with the participation of 2,327 children between 7 and 14 years old. In this experience the receptivity of teachers, improving their skills and knowledge are a guarantee for replication in children(AU)

¿Es el síndrome de apnea-hipoanea durante el sueño (SAHS) un factor de riesgo de enfermedad neurodegenerativa en el trastorno de conducta en sueño REM (RBD)? / No disponible

Introducción: Estudios epidemiológicos han observado una elevada prevalencia del RBD y SAHS en el anciano. El RBD se clasifica como idiopático y asociado a enfermedades neurodegenerativas. La presencia de SAHS en el RBD es frecuente (34-61 %), aunque parece que su gravedad es menor. Iranzo y Santamaría identificaron un subgrupo de pacientes con “pseudo-RBD”, que eran pacientes con SAHS severo exclusivamente. Objetivo: Determinar la prevalencia de SAHS en una muestra de pacientes que cumplen criterios clínicos y vídeo-PSG de RBD y cuantificar el riesgo de desarrollar una enfermedad neurodegenerativa. Material y métodos: 38 pacientes con diagnóstico de RBD y seguimiento durante varios años. Se observó que un 41,2% desarrollaron procesos neurodegenerativos. El diagnóstico de RBD y SAHS se realizó mediante vídeo-PSG. La cobertura estadística: 89,5% (34/38). El 68,4% hombres con edad media de 62,9 años. La prevalencia de SAHS fue del 64,7 %, del 55% en el grupo RBD idiopático frente al 78,5% en el grupo que desarrolló una enfermedad neurodegenerativa. Para llevar a cabo el análisis de los paciente se realizó un estudio observacional, cohorte. La implicación del SAHS se estudió mediante el Riesgo Relativo (RR). Definición de caso: persona con diagnóstico de RBD y SAHS que desarrolla una enfermedad neurodegenerativa. Resultados: Se obtuvo un RR del 2, con un IC del 95% (0,69-5,75), estadísticamente no significativo. Discusión y Conclusiones: En nuestra muestra se demostró una prevalencia y características del RBD congruentes con la literatura. La investigación no permitió demostrar una asociación estadísticamente significativa (AU)

Introduction: Epidemiological studies have observed a high prevalence of RBD and SAHS among the elderly. RBD qualifies as idiophatic and is associated with neurodegenerative diseases. Presence of SAHS in RBD is frequent (34-61 %), though it seems that its seriousness is minor. Iranzo and Santamaría identified a patient’s subgroup with "pseudo-RBD", who exclusively had severe SAHS. Our goal is to determine SAHS prevalence in a patients sample that meet the clinical criteria and RBD video-PSG, and on the other hand to quantify the risk of developing a neurodegenerative disease. Material and methods: 38 patients with RBD diagnosis and follow-up during a few years.We observed that 41.2% developed neurodegenerative diseases. Diagnosis of RBD and SAHS was performed by video-PSG. Statistical coverage: 89.5% (34/38). 68.4% men with mean age of 62.9 years. SAHS prevalence was 64.7 %, 55% for RBD idiophatic group, against 78.5% for the group that developed a neurodegenerative disease. To carry out the analysis, an observational cohort study was performed. Implication of SAHS was analyzed by means of Relative Risk (RR). Definition of case: it presents with diagnosis of RBD and SAHS that develops a neurodegenerative disease. Results: RR of 2 was obtained, with an IC of 95% (0.69-5.75), statistically not significant. Discussion and Conclusions:In our sample, RBD prevalence and characteristics were consistent with literature. Research did not allow proving a statistically significant association (AU)

[Minimally invasive posterior approach in total hip arthroplasty. Prospective randomised trial]. / Abordaje posterior mínimamente invasivo en artroplastia total de cadera. Estudio prospectivo y aleatorizado. Un año de seguimiento.

BACKGROUND: Our working hypothesis was that minimally invasive surgery was superior to conventional surgery for total hip arthroplasty procedure. We compared THR results in the minimally invasive posterior approach with THR results in the conventional posterior approach. METHODS: Prospective, randomised trial. Fifty patients were selected and then divided into two groups based on treatment (minimally invasive posterior approach or conventional posterior approach). DATA COLLECTED: Perioperative bleeding, postoperative pain, time of recovery, component orientation, complications and functional results. One year follow-up. RESULTS: No differences were found in blood loss, surgical time, component orientation, rate of complications or functional result. The minimally invasive lateral approach produced less postoperative pain and a faster recovery, with a shorter hospital stay and earlier walking-start, and a positive economic impact with 5% of the total process cost saved. CONCLUSIONS: Minimally invasive surgery permits less postoperative pain, faster recovery and a positive economic saving, without differences in the rest of the items studied.

Minimally invasive subvastus approach: improving the results of total knee arthroplasty: a prospective, randomized trial.

BACKGROUND: Minimally invasive knee arthroplasty seeks to diminish the problems of traditional extensile exposures aiming for more rapid rehabilitation of patients after surgery. QUESTIONS/PURPOSES: To determine if the subvastus approach results in less perioperative pain and blood loss, shorter hospital stay, and improved function at both early and long-term followup. METHODS: One hundred patients were enrolled in a prospective, randomized trial. Fifty were operated on using a minimally invasive subvastus approach and the other 50 by a conventional, peripatellar approach. Minimum followup was 3 years. A repeated-measures analysis of variance was used to compare the Knee Society score and range of motion during followup. RESULTS: The minimally invasive approach resulted in greater perioperative bleeding but no increase in transfusions. No differences were found in postoperative pain between groups nor did hospital stay show any differences. The range of motion on the third day after surgery was greater in the minimally invasive group. No differences were found in surgical time, femoral or tibial component orientation or outliers, or complication rates. Both Knee Society score and range of motion were superior using the minimally invasive subvastus approach during followup out to 36 months. CONCLUSIONS: The minimally invasive subvastus approach can result in improved long-term Knee Society scores and range of motion of total knee arthroplasty without increased risk of component malalignment, surgical time, or complication rate. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Estudio sobre la disminución de leprorreacciones en Fontilles desde la implantación del tratamiento con poliquimioteraia de la OMS respecto a tratamientos anteriores en los que se empleaban diferentes dosis de Rifampicina / No disponible

Se realizó un estudio descriptivo analítico con una muestra de 64 sujetos tratados en Fontilles, 30 de los cuales recibieron multiterapia de la OMS y 34 otros tratamientos en los que se empleaban diferentes dosis de rifampicina. El objetivo general del estudio fue comparar el número de leprorreacciones sufridas por la población tratada con multiterapia de la OMS con las leprorreacciones sufridas por la población tratada con otras dosis de rifampicina. En ambos grupos las leprorreacciones fueron frecuentes, con un 46,7% y un 70,6% respectivamente. Ambos grupos eran bastante similares en cuanto a sexo (mayor proporción de hombres que de mujeres), forma clínica (predominio de enfermos multibacilares con lepra lepromatosa), diferían en cuanto a carga bacilar, siendo ésta más elevada en el segundo grupo (un 73,5% tenían un índice Bacteriológico > ó = a 4 +, mientras que en el grupo tratado con multiterapia de la OMS este porcentaje era de 26,7%). Tras analizar el comportamiento de las distintas variables en cuanto a la ocurrencia de leprorreacciones, se realizó un análisis multivariante para eliminar posibles sesgos y se obtuvo una importante significación estadística para una carga bacilar elevada, también se observó significación para la variable sexo, no así para el tratamiento. Se analizó entonces el efecto del tratamiento por separado en hombres y mujeres, viéndose que los hombres que recibían otras pautas de rifampicina que las recomendadas por la OMS tenían seis veces más riesgo de sufrir leprorreacciones, no observándose diferencias estadísticamente significativas para las mujeres entre recibir uno u otro tratamiento (AU)

An analytical descriptive study with a simple of 64 sujects treated in Fontilles was made, 30 of whom received the WHO Multidrug Therapy and the other 34 treatments in which different doses of rifampicin were used. The general objective of the study was to compare the number of Leprosy Reactions suffered by the population treated with WHO Multidrug therapy, with the Leprosy Reactions suffered by the population treated with other doses of rifampicin. In both groups the leprosy reactions were frequent, (46,7% and a 70,6% respectively). Both groups were quite similar in terms of sex (greater proportion of men than women), clinical classification (predominance of multibacilary patients with lepromatous leprosy), differed in Bacterial Index, this being higher in the second group (73,5% had a Bacterial index > or = to 4 +, whereas in the group treated with WHO Multidrug Therapy the percentage was 26,7%). As for the occurrence of Leprosy Reactions and after analyzing the behavior of the different variables, a multivariant analysis was made to eliminate possible slants and an important statistical signification for an elevated Bacterial Index was obtained, a statistical signification was also observed for the sex variable, but not so for the treatment. The effect of the treatment on men and women was analyzed separately then, observing that those men who received doses of rifampicin other than those recommended by the WHO had six times more risk of undergoing Leprosy Reactions. Statistically significant differences were not observed for the women group (AU)

Rotura espontánea de bazo en un caso de leishmaniasis visceral / Spontaneous rupture of the spleen in a patient with visceral leishmaniasis

No disponible

Plancenta previa: estudio retrospectivo 1988-1992 / Placenta praevia: retrospective study 1988-1992

Analizar la incidencia, características obstétricas y complicaciones maternas de la placenta previa. Estudio retrospectivo y descriptivo de 150 casos atendidos entre 1988 y 1992 en 19.854 nacimientos vivos. Maternidad del Hospital "Dr. Adolfo Prince Lara", Puerto Cabello, Estado Carabobo. La incidencia fue de 0,76 por ciento (1 caso por cada 132 nacimientos), el grupo de edad predominó entre los 27 a 32 años (40,67 por ciento). El 79,33 por ciento (119 casos) fueron multíparas, 70 por ciento (105 casos) fueron embarazos de término. Complicaciones maternas más frecuentes: hemorragias 31,03 por ciento; rotura prematura de membranas 31,03 por ciento y trabajo de parto pretérmino 24,13 por ciento. El 78,67 por ciento terminó por cesárea. El 78 por ciento (114 neonatos) tuvieron peso > a 2 500 g. El 65,47 por ciento presentaron Apgar mayor igual 7 puntos, hubo 1 muerte materna. El manejo expectante de la plancenta previa, el ultrasonido diagnóstico y el uso de cesárea, han contribuido a disminuir la morbi-mortalidad materno-fetal

Angioplastia percutánea de aorta infrarrenal. Experiencia en The American British Cowdray Medical Center IAP / Percutaneous transluminal angioplasty of infrarenal aorta. Experience at the American British Cowdray Medical Center IAP

La angioplastia percutánea se desarrolló hace alrededor de 40 años y actualmente es uno de los tratamientos establecidos para restaurar el flujo sanguíneo en extremidades con isquemia crónica. Objetivo: Presentamos la experiencia en el Hospital ABC sobre el tratamiento con angioplastia percutánea de lesiones estenóticas de la aorta abdominal, así como un caso y la revisión de los criterios para efectuar estos procedimientos. Material y método: Estudio retrospectivo de los registros clínicos de los procedimientos realizados en el hospital, presentación de un caso y revisión de la literatura. Conclusiones: La angioplastia percutánea de lesiones estenóticas de aorta abdominal es un procedimiento mínimamente invasivo, seguro y con la misma efectividad que los procedimientos quirúrgicos, por lo que se considera el tratamiento de elección. Debe ser realizada en pacientes seleccionados y por un equipo de cirujanos vasculares y radiólogos para obtener los mejores resultados.