One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study

Cancer; Constipation; PainCàncer; Restrenyiment; DolorCáncer; Estreñimiento; DolorAbstract Objectives Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. Methods This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). Results A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. Conclusion The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.This study was sponsored by Kyowa Kirin Farmacéutica S.L., Spain. The funders participated in the design of the study and the drafting of the manuscript

Selective Implantation of Diamines for Cooperative Catalysis in Isoreticular Heterometallic Titanium-Organic Frameworks

This is the peer reviewed version of the following article: Selective Implantation of Diamines for Cooperative Catalysis in Isoreticular Heterometallic Titanium-Organic Frameworks, which has been published in final form at https://doi.org/10.1002/anie.202100176. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] We introduce the first example of isoreticular titanium-organic frameworks, MUV-10 and MUV-12, to show how the different affinity of hard Ti(IV) and soft Ca(II) metal sites can be used to direct selective grafting of amines. This enables the combination of Lewis acid titanium centers and available -NH, sites in two sizeable pores for cooperative cycloaddition of CO2 to epoxides at room temperature and atmospheric pressure. The selective grafting of molecules to heterometallic clusters adds up to the pool of methodologies available for controlling the positioning and distribution of chemical functions in precise positions of the framework required for definitive control of pore chemistry.This work was supported by the EU (ERC Stg Chem-fs-MOF 714122) and Spanish Government (CTQ2017-83486-P, RTI2018-098568-A-I00 & CEX2019-000919-M). E.L.-M. and S.T. thanks the Spanish Government for their Juan de la Cierva Fellowship (FJCI-2017-32956) and Ramon y Cajal contract (RYC-2016-1981), respectively. A.R.G. acknowledges funding from Generalitat Valencia (ACIF/2020/090)and Fondo Social Europeo. N.M.P. thanks the European Union for a Marie Sklodowska-Curie Global Fellowship (H2020MSCA-IF-2016-GF-749359-EnanSET) and to the "2020 Postdoctoral Junior Leader-Retaining Fellowship, la Caixa Foundation (ID 100010434 and fellowship code LCF/BQ/PR20/11770014)". F.G.C. acknowledges the support of a fellowship from "la Caixa" Foundation (ID 100010434 and the fellowship code LCF/BQ/PI19/11690011). S.N. thanks financial support by the Ministerio de Ciencia, Innovacion y Universidades (RTI 2018-099482-A-I00 project), Fundacion Ramon Areces (XVIII Concurso Nacional para la Adjudicacion de Ayudas a la Investigacion en Ciencias de la Vida y de la Materia, 2016) and Agencia Valenciana de la Innovacion (AVI-GVA, Carboagua project, INNEST/2020/111).López-Maya, E.; Padial, NM.; Castells-Gil, J.; Ganivet, CR.; Rubio-Gaspar, A.; García Cirujano, F.; Almora-Barrios, N.... (2021). Selective Implantation of Diamines for Cooperative Catalysis in Isoreticular Heterometallic Titanium-Organic Frameworks. Angewandte Chemie International Edition. 60(21):11868-11873. https://doi.org/10.1002/anie.2021001761186811873602

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis

Objectives: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. Methods: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. Results: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). Conclusions: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile

Antimicrobial Stewardship Programs Are Required in a Department of Surgery: "How" Is the Question A Quasi-Experimental Study: Results after Three Years

Objective: Our aim was to describe our antimicrobial stewardship program and the methodology based on the results in a surgical department. Methods: Our study was a quasi-experimental study conducted from January 1, 2009, through September 30, 2017. The site was the General and Digestive Surgery Department in a public primary referral center, the University Hospital of Getafe (Madrid, Spain). We implemented the antimicrobial stewardship program following a prospective audit and feedback model, with a surgeon incorporated into the manaagement group. We studied the deaths and 30-day re-admission rates, length of stay, prevalence of gram-negative bacilli, meropenem resistance, and days of treatment with meropenem. Results: After three years of the program, we recorded a significant decrease in Pseudomonas aeruginosa prevalence, a significant increase in Klebsiella pneumoniae prevalence, a decrease in meropenem resistance, and a reduction in meropenem days of treatment. Conclusions: Antimicrobial stewardship programs have a desirable effect on patients. In our experience, the program team should be led by a staff from the particular department. When human resources are limited, the sustainability, efficiency, and effectiveness of interventions are feasible only with adequate computer support. Finally, but no less important, the necessary feedback between the prescribers and the team must be based on an ad hoc method such as that provided by statistical control charts, a median chart in our study.MINECO ID project (TIN 2013-45491-R)2.150 JCR (2020) Q3, 125/211 Surgery0.773 SJR (2020) Q2, 135/293 Infectious DiseasesNo data IDR 2020UE

Programa de optimización de antibióticos en un servicio de Cirugía General y Digestiva: efecto sobre prescripción de meropenem en sus dos primeros de implantación

La resistencia antimicrobiana es una de las alertas sanitarias actuales. Su emergencia se relaciona con el aumento de consumo de antibióticos, especialmente significativo en carbapenémicos alcanzado casi un 40% de aumento, y en su uso no óptimo, llegando al 30-50% en el ámbito hospitalario. Las estrategias para la lucha contra la resistencia se dirigen al desarrollo de nuevos antibióticos, a medidas de control-prevención de infección y la optimización de su uso, donde encontramos los Programas de Optimización de Antibióticos (PROA). Actualmente se apela a la implicación de los cirujanos en este compromiso, siendo escasas las experiencias PROA centradas en Cirugía General y Digestiva. Esta es la primera experiencia nacional al respecto. En nuestro hospital se creó un grupo PROA (estrategia de auditoría prospectiva y feedback), incluyendo a un cirujano general y digestivo. El grupo revisa los tratamientos antimicrobianos y realiza recomendaciones sobre selección, dosis, duración o desescalado, que el especialista en cirugía transmite verbalmente al responsable, que la acepta o no. Se revisaron todos los pacientes ingresados consecutivamente en el servicio de Cirugía General y Digestiva de nuestro centro desde 01/2009 hasta 09/2016, en dos periodos: Pre-PROA: de 01/01/2009 a 30/09/2014, retrospectiva. Post-PROA: de 01/10/2014 a 30/09/2016, prospectiva. Los datos se recogieron mediante una base de datos informatizada (WASPSS: Wise Antimicrobial Stewardship Program), que integra base de datos informatizadas previamente, con capacidad de lectura retrospectiva y sostenible automáticamente. Se recogió la evolución temporal de la prescripción de carbapenémicos, medida en días de tratamiento (DOT × 1.000 ocupaciones/cama/día), en ambos periodos a estudio, en el servicio de Cirugía General y Digestiva. En la figura se muestra la evolución temporal de DOT de meropenem en el servicio de Cirugía General y Digestiva en periodo pre-PROA vs post-PROA. Se objetiva un descenso de nivel y tendencia en la prescripción de meropenem tras la implantación de PROA en nuestro servicio de Cirugía General y Digestiva. Conocer la situación de partida de la unidad/centro donde se va a implantar un PROA es fundamental para su éxito. En nuestro caso documentar el creciente uso de carbapenémicos nos permitió enfocar la estrategia hacia este objetivo. Según la literatura, los PROA han demostrado disminuir y mejorar el uso de antibióticos, así como disminuir los efectos adversos. En nuestro caso, la implantación de PROA produjo un descenso de la prescripción de meropenem en el servicio de Cirugía, objetivado desde el primer momento de su implantación. La representación mediante serie temporal descarta las modificaciones se deban a un cambio gradual en el servicio. El cambio de la prescripción no se debió al cambio en la prevalencia de microorganismos. El papel del cirujano en el equipo PROA es factor relevante en los resultados obtenidos sobre la monitorización 0009-739X – See front matter © 2017 Elsevier España, S.L. Todos los derechos reservados antibiótica. Es necesario el compromiso de los especialistas en Cirugía para hacer hincapié en el uso racional de los antimicrobianos y para promover la mejora continua de la práctica clínica quirúrgica.Sin financiación0.841 JCR (2017) Q4, 170/200 SurgeryUE

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia.

We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes 0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3–4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice

Exploring Health Science Students' Notions on Organ Donation and Transplantation: A Multicenter Study.

The knowledge acquired during university education about organ donation and transplantation (ODT) decisively influences the information future health professionals transmit. This is important in ODT where the participation of the general public is essential to obtain organs. To determine notions of Spanish medicine and nursing students on ODT and its relationship with attitude toward ODT. and design. We conducted a sociologic, multicenter, and observational study. The population for our study consisted of medical and nursing students in Spanish universities. Our database was the Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. Our sample consisted of 9598 medical and 10,566 nursing students (99% confidence interval; precision of ±1%), stratified by geographic area and year of study. The completion rate for our study was 90%. Only 20% (n=3640) of students thought their notions on ODT were good; 41% (n=7531) thought their notions were normal; 36% (n=6550) thought their notions were scarce. Comparing groups, there were differences between those who believed that their notions on ODT were good (44% nursing vs 56% medical students; P  Only 20% of Spanish medical and nursing students thought their notions on ODT were good. Having good knowledge is related to a favorable attitude towards ODT. Receiving specific information on the subject could improve their knowledge about ODT during their training