El registro continuado de los efectos adversos mejora los resultados quirúrgicos / Continuous monitoring of adverse effects improves surgical outcomes

Antecedentes: Se ha debatido mucho sobre las ventajas e inconvenientes del uso de bases administrativas o de registros clínicos en los programas de mejora de la atención médica. El objetivo de este estudio ha sido revisar la implementación y los resultados de una política de evaluación continua, mediante un registro mantenido por profesionales de un Servicio de Cirugía. Material y métodos: Se incluyeron, de forma prospectiva, todos los pacientes ingresados en el servicio entre los años 2003 y 2022. Se anotaron todos los efectos adversos (EA) acaecidos durante el ingreso, la estancia en centros de convalecencia o en su domicilio durante un periodo mínimo de 30 días tras el alta. Resultados: De 60.125 registros, en 16.802 (27,9%) se registraron 24.846 EA. Hubo un aumento progresivo del número de EA registrados por ingreso (1,17 en 2003 vs. 1,93 en 2022) con una disminución de 26% de los registros con EA (35% en 2003 hasta 25,8% en 2022), de 57,5% en las reoperaciones (de 8 a 3,4%, respectivamente), y de 80% en la mortalidad (de 1,8 a 1%, respectivamente). Es de remarcar la reducción significativa de los EA graves, observada entre los años 2011 y el 2022 (56 vs. 15,6%). Conclusión: Un registro prospectivo de EA creado y mantenido por profesionales del servicio, junto con la presentación y discusión abierta y trasparente de los resultados, produce una mejora sostenida de los resultados en un servicio quirúrgico de un hospital universitario.(AU)

Background: There has been significant debate about the advantages and disadvantages of using administrative databases or clinical registries in healthcare improvement programs. The aim of this study was to review the implementation and outcomes of an accountability policy through a registry maintained by professionals of the surgical department.Materials and methods: All patients admitted to the department between 2003 and 2022 were prospectively included. All adverse events (AEs) occurring during the admission, convalescent care in facilities, or at home for a minimum period of 30 days after discharge were recorded. Results: Out of 60,125 records, 24,846 AEs were documented in 16,802 cases (27.9%). There was a progressive increase in the number of AEs recorded per admission (1.17 in 2003 vs. 1.93 in 2022) with a 26% decrease in entries with AEs (from 35% in 2003 to 25.8% in 2022), a 57.5% decrease in reoperations (from 8.0% to 3.4%, respectively), and an 80% decrease in mortality (from 1.8% to 1%, respectively). It is noteworthy that a significant reduction in severe AEs was observed between 2011 and 2022 (56% vs. 15.6%). Conclusion: A prospective registry of AEs created and maintained by health professionals, along with transparent presentation and discussion of the results, leads to sustained improvement in outcomes in a surgical department of a university hospital.(AU)

Childhood abuse and opioid prescription use in adulthood: Differences between non-Hispanic Whites and non-Hispanic Blacks in the United States.

Despite the rapid rise in opioid prescription medication usage, little research has examined the role of early life adversity, such as childhood abuse, particularly in the context of race, in opioid prescription usage in adulthood. Guided by the life course perspective, the current study investigates whether experiencing childhood abuse increases the risk of opioid prescription use in adulthood and whether this association varies by race. Data were sourced from the second wave of the Midlife in the United States (MIDUS) study (2004-2005). The analytic sample consisted of two groups: non-Hispanic Whites (n = 714) and non-Hispanic Blacks (n = 151). Opioid prescription use was identified from the participants' medication list using the MULTUM Lexicon Drug Database Classification System. Three types of childhood abuse-emotional, physical, and sexual-were assessed via summary scales derived from the Childhood Trauma Questionnaire. The results indicate a significant interaction between childhood physical abuse and race. Among non-Hispanic Whites, higher exposure to physical abuse during childhood was associated with greater odds of opioid prescription use in adulthood, even after adjusting for chronic pain, physical and mental health, and sociodemographic characteristics. However, the association between childhood physical abuse and opioid prescription use in adulthood was non-significant among non-Hispanic Black individuals. These findings underscore the long-term adverse health effects of physical abuse in childhood, particularly for non-Hispanic Whites, and suggest support for developing and implementing tailored intervention strategies.

Efectos adversos de la radiación cósmica en personal aeronáutico: Revisión Sistemática / Side effects of cosmic radiation on aeronautic personnel: Systematic Review

Introducción: El personal de vuelo y astronautas estan sometidos a exposición ocupacional a radiación cósmica que podría producir la aparición de efectos patológicos. Hasta el momento, la evidencia disponible se orienta al estudio de patologías específicas sin recoger todos los posibles efectos adversos.Método: Revisión sistemática (RS) de la literatura publicada hasta enero 2023. Las bases de datos consultadas fue-ron PubMed, EMBASE, LILACS y Cochrane. Los descriptores utilizados fueron “Adverse effects”, “Cosmic Radiation”, y “Aeronautic”. Se incluyeron estudios con información sobre eventos adversos de la radiación cósmica en trabaja-dores expuestos. Se evaluó la calidad de la evidencia.Resultados: Se incluyeron 27 estudios (11 RS y 16 observacionales). Algunos estudios encontraron que los traba-jadores aeronáuticos tenían mayor riesgo neoplásico (cáncer de mama, cerebro, leucemia y melanoma) y de cata-ratas nucleares. Sin embargo, otros estudios no describieron el desarrollo de enfermedades neoplásicas ni otras patologías estudiadas (genéticas, ginecológicas o cardiovasculares) por radiaciones ionizantes. La calidad de las RS (AMSTAR–2) fue críticamente baja en la mayoría, y los estudios observacionales (STROBE) obtuvieron una media de alrededor del 72%.Conclusiones: La evidencia disponible no permite encontrar causalidad directa entre exposición a radiación cós-mica y aparición de patologías en personal expuesto. Se consideran necesarios nuevos estudios bien diseñados (AU)

Introduction: Aircrew and astronauts are subject to cosmic radiation as part of their jobs and could be associated with various pathological effects. Until now, available evidence is oriented to the study of specific pathologies with-out consideration of all possible adverse effects.Method: A systematic review (SR) from literature found until 2023 January. The databases included were PubMed, EMBASE, LILACS and Cochrane. The following descriptors used “Adverse effects” “Cosmic Radiation” and “Aeronau-tic”. Included studies had information on adverse effects of cosmic radiation in exposed workers. We assessed the quality of the evidence.Results: 27 studies were included (11 SR and 16 observational). Some articles determined that aeronautic person-nel have a higher cancer risk (breast, brain, leukemia and melanoma) and nuclear cataracts. However, other studies did not describe neoplastic diseases or other studied pathologies (genetics, gynecological, cardiovascular) due to ionizing radiation. The quality of the SR (AMSTAR-2) was critically low in the vast majority and the average quality for observational studies (STROBE) around 72%.Conclusions: Available evidence does not allow us to find direct causality between exposure to cosmic radiation and the appearance of pathologies in exposed personnel. New well-designed studies considered necessary. (AU)

[Response to the letter to the editor of "Commentary on the COVID-19 mRNA vaccine reactogenicity study"]. / Respuesta a la carta al editor de "Comentario al Estudio de reactogenicidad de la vacuna ARNm de COVID-19".

Dear Editor, Our study aims to compare the short-term adverse effects and their consequences between the RNAm vaccines Commirnaty® (Pfizer) and Spikevax® (Moderna), as well as these short-term adverse effects and their consequences between the first and second doses of these vaccines with each other. Possible long-term adverse effects were not the subject of our study….

Querido editor, Nuestro estudio tiene por objetivo, comparar los efectos adversos a corto plazo y sus consecuencias entre las vacunas RNAm, Commirnaty® (Pfizer) y Spikevax® (Moderna), así como, estos efectos adversos a corto plazo y sus consecuencias entre la primera y la segunda dosis de las citadas vacunas entre sí. Los posibles efectos adversos a largo plazo no eran objeto de nuestro estudio….

Experiencia ibérica con PASCAL para la reparación percutánea borde a borde en insuficiencia mitral / Iberian experience with PASCAL transcatheter edge-to-edge repair for mitral valve regurgitation

Introducción y objetivos: PASCAL es un dispositivo novedoso de terapia mitral transcatéter basada en la reparación borde a borde. Algunas características únicas podrían tener un impacto relevante en sus resultados. Hay pocos datos sobre los resultados clínicos en registros de la vida real. El objetivo de este estudio es publicar la experiencia ibérica precoz (centros de España y Portugal) del sistema PASCAL. Métodos: Se incluyó prospectivamente a los pacientes tratados consecutivamente de insuficiencia mitral (IM) grave sintomática en 10 centros. El objetivo primario de eficacia fue el éxito técnico y el grado de regurgitación al alta. El objetivo primario de seguridad fueron los eventos adversos mayores (MAE) a 30 días. Resultados: Se incluyó a 68 pacientes (75 [68-81] años, 38% mujeres, EuroSCORE II 4,5%). La IM fue degenerativa en el 25% de los casos, funcional en el 65%, y mixta en el 10%. El 71% de pacientes estaban en clase funcional New York Heart Association (NYHA)≥III. El éxito técnico fue del 96% y la captura independiente se usó en el 73% de los procedimientos. Toda la población tratada obtuvo una IM al alta≤2+ (100%) y no hubo muertes intrahospitalarias. A los 30 días, los MAE fueron del 5,9%, la mortalidad global del 1,6%, el 98% estuvieron en clase NYHA≤II y el 95% tuvieron IM≤2+ (p <0,001). Conclusiones: El sistema PASCAL de terapia transcatéter mitral fue efectivo y seguro, con elevado éxito técnico y baja tasa de MAE. A los 30 días la IM se redujo significativamente, y hubo una mejoría en la clase funcional.(AU)

Introduction and objectives: The PASCAL system is a novel device for transcatheter mitral valve repair based on the edge-to-edge concept. The unique features of this device might have a relevant impact on the repair outcomes. There are few data on clinical outcomes in real-life registries. The aim of this study was to report the early Iberian experience (Spain and Portugal) of the PASCAL system. Methods: Procedural and 30-day outcomes were investigated in consecutive patients with symptomatic severe mitral regurgitation (MR) treated with the PASCAL system at 10 centers. Primary efficacy endpoints were technical success and degree of residual MR at discharge. The primary safety endpoint was the rate of major adverse events (MAE) at 30 days. Results: We included 68 patients (age, 75 [68-81] years; 38% women; EuroSCORE II 4.5%). MR etiology was degenerative in 25%, functional in 65%, and mixed in 10%. A total of 71% of patients were in New York Heart Association (NYHA) functional class≥III. Technical success was achieved in 96% and independent capture was used in 73% of procedures. In the treated population, MR at discharge was≤2+ in 100%, with no in-hospital deaths. At 30 days, the MAE rate was 5.9%, the all-cause mortality rate was 1.6%, 98% were in NYHA functional class≤II, and 95% had MR≤2+ (P<.001). Conclusions: Transcatheter mitral valve repair with the PASCAL system was safe and effective, with high procedural success and low rates of MAE. At 30 days, MR was significantly reduced, with a significant improvement in functional status.(AU)

Corticosteroid safety in COVID-19 patients: a pharmacovigilance study / Seguridad de corticoesteroides en pacientes con COVID-19: un estudio de farmacovigilancia

The use of oral and intravenous corticosteroids as a treatment for SARS-CoV-2 infection has been shown to inhibit the exaggerated inflammatory response, reducing symptoms and days of hospitalization of patients. However, its use is controversial because not enough clinical studies have been made to verify the safety of the drugs. Objective: To assess the safety profile of corticosteroids treatment, at high and low doses, in suspected or confirmed patients with COVID-19, determining the most frequent side effects in patients, and assessing whether the administration of the drugs represents a greater benefit than the risk of presenting these effects. Methods: Ambispective study of active pharmacovigilance at a cohort of confirmed or suspected COVID-19 patients, treated with intravenous and oral corticosteroids. 366 patients were evaluated and divided into 3 groups: use of methylprednisolone (155 mg average) every 24 hours for 3 days, dexamethasone (6 mg) every 24 hours for 10 days, and a control group. Results: The distribution of the cases with hyperglycemia was 33 in high doses and 82 with low doses of corticosteroids and both high and low doses have a similar distribution in cases of infections. When evaluating the harshness and severity of hyperglycemia in the two groups with corticosteroids, it is observed that patients with high doses present more harsh (48%). In case of harshness and severity of infections it is observed that patients with high doses present more harsh (62%) and more severe (79%) cases than those who were administered low doses. (AU)

El uso de corticoides orales e intravenosos como tratamiento para la infección por SARS-CoV-2 ha demostrado inhibir la respuesta inflamatoria exagerada, reduciendo los síntomas y los días de hospitalización de los pacientes. Sin embargo, su uso es controvertido porque no se han realizado suficientes estudios clínicos para verificar la seguridad de los medicamentos. Objetivo: Evaluar el perfil de seguridad del tratamiento con corticoides, a dosis altas y bajas, en pacientes con sospecha o confirmación de COVID-19, determinando los efectos secundarios más frecuentes en los pacientes, y valorando si la administración de los fármacos representa un mayor beneficio que el riesgo de presentar estos efectos. Métodos: Estudio ambispectivo de farmacovigilancia activa en una cohorte de pacientes confirmados o sospechosos de COVID-19, tratados con corticoides intravenosos y orales. Se evaluaron 366 pacientes y se dividieron en 3 grupos: uso de metilprednisolona (155 mg promedio) cada 24 horas por 3 días, dexametasona (6 mg) cada 24 horas por 10 días y un grupo control. Resultados: La distribución de los casos con hiperglucemia fue de 33 casos usando dosis altas y 82 con dosis bajas de corticoides, tanto las dosis altas como las bajas tienen la misma distribución en los casos de infecciones. Al evaluar la severidad y gravedad de la hiperglucemia en los dos grupos con corticoides, se observa que los pacientes con dosis altas presentan mayor gravedad (48%). En caso de severidad y gravedad de las infecciones se observa que los pacientes con dosis altas presentan casos más graves (62%) y más severos (79%) que los que recibieron dosis bajas. (AU)

Évaluation de la prescription et de l'utilisation des benzodiazépines dans la ville de Sidi Bel-Abbès / Evaluation of the prescription and use of benzodiazepines in Sidi Bel-Abbes city

Introduction :Une forte consommation des benzodiazépines (BZDs) a été remarquée en dehors parfois des règles de recommandations de prescription, ce qui rend leur consommation un problème majeur de santé publique. La présente étude a eu pour objectif d'évaluer la prescription et l'usage des BZDs dans la ville de Sidi Bel-Abbès. Méthodes-Il s'agissait d'une étude descriptive transversale réalisée du 01 Février 2018 au 30 Juin 2018 évaluant la prescription et l'usage des BZDs dans la ville de Sidi Bel-Abbès au moyen d'un questionnaire distribué aux patients de l'hôpital psychiatrique, du service de psychiatrie du CHU et aux pharmaciens d'officine.Le critère de jugement principal était l'évaluation de la prescription et de l'utilisation des BZDs dans cette ville. La saisie et l'analyse des données ont été réalisées par le logiciel SPSS. Résultats-Au total, 353 patients traités au moins par une BZD ont été inclus dont 178 hommes. Le taux de prescription des BZDs était de 1.10, des jeunes (59,77 %) et des personnes mariées (60,34%) constituaient les consommateurs privilégiés. La prescription était l'apanage des psychiatres, en monothérapie (07,42%), la molé cule la plus fréquemment prescrite était le Bromazépam (31,07%) et la prise noc turne était la plus importante (49,01%). Les BZDs étaient utilisées pour combattre l'insomnie (25,21%), l'anxiété (16,43%), pour une durée de plus d'une année (57,79 %). Conclusion-La prescription et l'utilisation des BZDs dans la ville de Sidi Bel-Abbès s'est avérée importante. L'insomnie et l'anxiété constituaient les principales raisons de leur utilisation, et le Bromazépam était la molécule la plus fréquemment utilisée .

Introduction-A high consumption of benzodiazepines (BZDs) has been noticed so metimes outside the rules of prescription recommendations, which makes their consumption a major public health problem. The present study aimed to evaluate the prescription and use of BZDs in Sidi Bel-Abbès city. Methods-: This was a descriptive cross-sectional study carried out from February 01st, 2018 to June 30th, 2018 evaluating the prescription and use of BZDs in of Sidi Bel-Abbès by means of a questionnaire distributed to patients from the psychiatric hospital, the CHU psychiatry department and community pharmacists. The primary endpoint was the assessment of the prescription and use of BZDs in this city. Data entry and analysis were performed using SPSS software. Results-A total of 353 patients treated with at least one BZD were included, including 178 men. The prescription rate of BZDs was 1.10, young people (59.77%) and married people (60.34%) were the privileged consumers. The prescription was the prerogative of psychiatrists, in monotherapy (07.42%), the molecule most frequent ly prescribed was Bromazepam (31.07%) and night intake was the most important (49.01%). BZDs were used to combat insomnia (25.21%), anxiety (16.43%), for a period of more than a year (57.79%). Conclusion-The prescription and use of BZDs in Sidi Bel-Abbès has proven to be important. Insomnia and anxiety were the main reasons for their use, and Bromazepam was the most molecule frequently used.

Terapias cuádruples son superiores a terapia triple estándar en primera línea de erradicación de Helicobacter pylori en Chile / Quadruple therapies are superior to standard triple therapy for Helicobacter pylori first-line eradication in Chile

Introducción: La infección por Helicobacter pylori afecta aproximadamente al 70% de la población chilena. Es un problema de salud pública cuyo tratamiento de erradicación forma parte de políticas públicas en Chile. Objetivos: Caracterizar los esquemas de erradicación de primera línea de H. pylori más utilizados en nuestro medio y evaluar su eficacia. Métodos: Se realizó un estudio observacional retrospectivo donde, en pacientes con infección por H. pylori certificada, se evaluó el esquema de erradicación indicado por el médico tratante, su eficacia, adherencia y efectos adversos. Resultados: Se analizaron 242 pacientes y 4 esquemas de erradicación; terapia triple estándar, terapia dual, concomitante y cuadriterapia con bismuto. Se observaron tasas de erradicación de 81,9% (IC 95% 74,44-87,63), 88,5% (IC 95% 73,13-95,67), 93,7% (IC 95% 78,07-98,44) y 97,6% (IC 95% 84,81-99,67) respectivamente, siendo más eficaces la terapia concomitante (RR: 1,14; IC 95% 1,01-1,29; p=0,028) y cuadriterapia con bismuto (RR: 1,19; IC 95% 1,09-1,31; p<0,001) que la triple terapia estándar. La tasa de efectos adversos reportados fue de 58,5% (IC 95% 50,66-65,92), 35,4% (IC 95% 24,6-48,11), 22,9% (IC 95% 11,81-37,14) y 63,4% (IC 95% 47,8-76,64), para la terapia triple estándar, dual, concomitante, y cuádruple con bismuto, respectivamente. La terapia dual y concomitante tuvieron menos efectos adversos en comparación con la terapia estándar. Conclusiones: Las cuadriterapias son superiores a la triple terapia estándar por lo que deberían ser consideradas como tratamiento de primera línea en Chile. La terapia dual es promisoria. Más estudios serán requeridos para determinar qué esquemas son más costo-efectivos.(AU)

Introduction: Helicobacter pylori infection affects approximately 70% of the Chilean population. It is a public health problem whose eradication treatment is part of the explicit health guarantees in Chile. Objectives: Characterize the most widely used H. pylori first-line eradication therapies in our environment and evaluate their efficacy. Methods: A retrospective observational study was carried out where, in patients with certified H. pylori infection, the eradication therapy indicated by the treating physician, its efficacy, adherence and adverse effects, in addition to the eradication certification method used, were evaluated. Results: 242 patients and 4 main therapies were analyzed: standard triple therapy, dual therapy, concomitant therapy, and bismuth quadruple therapy. Eradication rates of 81.9% (95% CI 74.44–87.63), 88.5% (95% CI 73.13–95.67), 93.7% (95% CI 78.07–98.44) and 97.6% (95% CI 84.81–99.67) were observed respectively, with concomitant therapy (RR: 1.14; 95% CI 1.01–1.29; p=.028) and quadruple therapy with bismuth (RR: 1.19; 95% CI 1.09–1.31; p<.001) being significantly more effective than standard triple therapy. Regarding the rate of reported adverse effects, it was 58.5% (95% CI 50.66–65.92), 35.4% (95% CI 24.6–48.11), 22.9% (95% CI 81–37.14) and 63.4% (95% CI 47.8–76.64), having the dual and concomitant therapy significantly fewer adverse effects compared with standard therapy. Conclusions: Quadruple therapies are superior to standard triple therapy and should be considered as first-line treatment in Chile. Dual therapy is promising. More studies will be required to determine which therapies are most cost-effective.(AU)

Reacción cútanea debida a remdesivir en paciente con enfermedad por SARS-CoV-2 / Skin reaction due to remdesivir in a patient with SARS-CoV-2 disease

En diciembre de 2019 se detectó por primera vez en la ciudad china de Wuhan una nueva enfermedad infecciosa con el nombre oficial de COVID-19, causada por un nuevo tipo de coronavirus denominado virus SARS-CoV-2, la infección se ha propagado rápida y extensamente por todo el mundo, por lo que el 11 de marzo de 2020 la Organización Mundial de la Salud la declaró pandemia. Al tratarse de una nueva infección, no existe por el momento evidencia que permita recomendar un tratamiento específico, en la actualidad el único medicamento con indicación autorizada por la Agencia Europea de Medicamentos (EMA) es el remdesivir. A continuación presentamos el caso de una reacción adversa a remdesivir, si bien no fue grave, cabe destacar la importancia de notificar efectos adversos y más en medicamentos novedosos como este. (AU)

In December 2019, a new infectious disease with the official name of COVID-19 was detected for the first time in the Chinese city of Wuhan, caused by a new type of coronavirus called SARS-CoV-2 virus, the infection has spread rapidly and widely throughout the world, which is why on March 11, 2020, the World Health Organization declared it a pandemic. As it is a new infection, there is currently no evidence to recommend a specific treatment, currently the only drug with an indication authorized by the European Medicines Agency (EMA) is remdesivir.We present the case of an adverse reaction to remdesivir, although it was not serious, it is worth highlighting the importance of reporting adverse effects and more in novel drugs like this one. (AU)

Late effects of high-dose methotrexate treatment in childhood cancer survivors-a systematic review.

BACKGROUND: High-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m2 body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking. METHOD: We conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262). RESULTS: We included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision. CONCLUSIONS: CCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX.

Long-term Outcomes of Adults With Tricuspid Regurgitation Following Transcatheter Atrial Septal Defect Closure.

BACKGROUND: Functional tricuspid regurgitation (TR) is a common pathophysiologic condition in adults with ostium secundum atrial septal defect (ASD). The aim of this study was to evaluate long-term outcomes following transcatheter ASD closure, which have not been well studied among patients with significant TR. METHODS: We reviewed consecutive adult patients who underwent transcatheter ASD closure at Toronto General Hospital, Ontario, Canada, from 1998 to 2016. We linked our hospital registry with Ontario population-based health administrative databases to collect longitudinal data on inpatient and outpatient health care utilisation and vital status. RESULTS: In this cohort study of 949 patients, 199 (22%) had moderate to severe TR before transcatheter ASD closure. A significant proportion of patients (61%) showed improvement in TR severity to at least mild TR after ASD intervention. At a median follow-up of 10.9 years, patients with baseline mild or no TR, compared with those with greater than moderate TR, had significantly lower rates of all-cause mortality (6.8 vs 22.5 per 1000 person-years [PY]; P < 0.001), composite hospitalisation for atrial fibrillation (AF) or heart failure (HF) (22.3 vs 49.1 per 1000 PY; P < 0.001), and new onset of AF (10.4 vs 20.2 per 1000 PY; P = 0.002) and HF (5.0 vs 9.2 per 1000 PY; P = 0.039). Preprocedural TR was independently associated with higher all-cause mortality (adjusted hazard ratio 1.69, 95% confidence interval 1.08-2.62). CONCLUSIONS: TR severity was independently associated with a higher risk of mortality and morbidity. Further investigation of earlier device closure or concomitant tricuspid valve intervention may be of interest.

Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies.

Importance: Meta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associations between hormonal contraceptive use and adverse health outcomes has not been quantified in aggregate. Objective: To grade the evidence from meta-analyses of randomized clinical trials (RCTs) and cohort studies that assessed the associations between hormonal contraceptive use and adverse health outcomes among women. Data Sources: MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to August 2020. Search terms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis. Evidence Review: The methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, version 2, which rated quality as critically low, low, moderate, or high. The Grading of Recommendation, Assessment, Development and Evaluations approach was used to assess the certainty of evidence in meta-analyses of RCTs, with evidence graded as very low, low, moderate, or high. Evidence of associations from meta-analyses of cohort studies was ranked according to established criteria as nonsignificant, weak, suggestive, highly suggestive, or convincing. Results: A total of 2996 records were screened; of those, 310 full-text articles were assessed for eligibility, and 58 articles (13 meta-analyses of RCTs and 45 meta-analyses of cohort studies) were selected for evidence synthesis. Sixty associations were described in meta-analyses of RCTs, and 96 associations were described in meta-analyses of cohort studies. Among meta-analyses of RCTs, 14 of the 60 associations were nominally statistically significant (P ≤ .05); no associations between hormonal contraceptive use and adverse outcomes were supported by high-quality evidence. The association between the use of a levonorgestrel-releasing intrauterine system and reductions in endometrial polyps associated with tamoxifen use (odds ratio [OR], 0.22; 95% CI, 0.13-0.38) was graded as having high-quality evidence, and this evidence ranking was retained in the subgroup analysis. Among meta-analyses of cohort studies, 40 of the 96 associations were nominally statistically significant; however, no associations between hormonal contraceptive use and adverse outcomes were supported by convincing evidence in the primary and subgroup analyses. The risk of venous thromboembolism among those using vs not using oral contraception (OR, 2.42; 95% CI, 1.76-3.32) was initially supported by highly suggestive evidence, but this evidence was downgraded to weak in the sensitivity analysis. Conclusions And Relevance: The results of this umbrella review supported preexisting understandings of the risks and benefits associated with hormonal contraceptive use. Overall, the associations between hormonal contraceptive use and cardiovascular risk, cancer risk, and other major adverse health outcomes were not supported by high-quality evidence.

Mechanical vs Bioprosthetic Aortic Valve Replacement in Patients Younger Than 70 Years of Age: A Hazard Ratio Meta-analysis.

BACKGROUND: The choice between mechanical valves (MVs) and bioprosthetic valves (BVs) in patients undergoing aortic valve surgery is complex, requiring a balance between the inferior durability of BV and the indicated long-term anticoagulation therapy with MV. This is especially challenging in the middle age group (< 70 years), which has seen an increased use of BV over recent years. METHODS: A meta-analysis of randomised controlled trials (RCTs), observational studies using propensity score matching (PSM) and inverse probability weighting (IPW) was conducted to examine the clinical outcomes of patients < 70 years of age undergoing aortic valve replacement. The primary outcome was overall long-term mortality. Secondary outcomes included bleeding events, reoperation, systemic thromboembolism, and cerebrovascular accident. RESULTS: Fifteen studies (1 RCT, 12 PSM studies, and 2 IPW studies; aggregated sample size 16,876 patients) were included. Median follow-up was 7.8 years. Mortality was higher with BVs vs MVs (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.00-1.49), as was reoperation (HR 3.05, 95% CI 2.22-4.19). Bleeding risk was lower with BVs (HR 0.58, 95% CI 0.48-0.69), and the risk of stroke was similar in both valve types (HR 0.96, 95% CI 0.83-1.11) CONCLUSIONS: This broadest meta-analysis comparing BV and MV suggests a survival benefit for MVs in patients < 70 years of age. This should lead to reassessment of current patterns used in the choice of valves for patients < 70 among the cardiothoracic surgery community.

Evaluating patient-reported symptoms and late adverse effects following completion of first-line chemotherapy for ovarian cancer using the MOST (Measure of Ovarian Symptoms and Treatment concerns).

OBJECTIVES: Knowledge on the course of symptoms patients with ovarian cancer experience is limited. We documented the prevalence and trajectories of symptoms after first-line chemotherapy using the Measure of Ovarian Symptoms and Treatment concerns (MOST). METHODS: A total of 726 patients who received platinum-based chemotherapy for ovarian cancer were asked to complete the MOST every 3 months, beginning 6 months post-diagnosis and continuing for up to 4 years. We used descriptive statistics to examine temporal changes in MOST-S26 index scores for disease or treatment-related (MOST-DorT), neurotoxicity (MOST-NTx), abdominal (MOST-Abdo), and psychological (MOST-Psych) symptoms, and wellbeing (MOST-Wellbeing) and selected individual symptoms. We used group-based trajectory models to identify groups with persistently poor symptoms. RESULTS: The median MOST-Abdo, MOST-DorT and MOST-Wellbeing score were worst at chemotherapy-end but improved and stabilised by 1, 3 and 12 months after treatment, respectively. The median MOST-NTx score peaked at 1 month after treatment before improving, while the median MOST-Psych score did not change substantially over time. Long-term moderate-to-severe fatigue (32%), trouble sleeping (31%), sore hands and feet (21%), pins and needles (20%) and anxiety (18%) were common. Trajectory models revealed groups of patients with persistent symptoms had MOST-DorT scores above 30 and MOST-NTx scores above 40 at treatment-end. CONCLUSIONS: Although many patients report improvements in symptoms by 3 months after first-line chemotherapy for ovarian cancer, patients who score > 30/100 on MOST-S26-DorT or > 40/100 on MOST-S26-NTx at the end of chemotherapy are likely to have persistent symptoms. The MOST could triage this at-risk subset for early intervention.

Long-term Outcomes of Minimally Invasive Versus Open Abdominoperineal Resection for Rectal Cancer: A Single Specialized Center Experience.

BACKGROUND: Randomized studies have validated laparoscopic proctectomy for the treatment of rectal cancer as noninferior to an open proctectomy, but most of those studies have included sphincter-preserving resections along with abdominoperineal resection. OBJECTIVE: This study aimed to compare perioperative and long-term oncological outcomes between minimally invasive and open abdominoperineal resection. DESIGN: This study is a retrospective analysis of a prospectively maintained database. SETTINGS: The study was conducted in a single specialized colorectal surgery department. PATIENTS: All patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2016 were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the perioperative and long-term oncological outcomes. RESULTS: We included 452 patients, 372 in the open group and 80 in the minimally invasive group, with a median follow-up time of 74 months. There were significant differences between the groups in terms of neoadjuvant radiation treatment (67.5% of the open versus 81.3% of the minimally invasive group, p = 0.01), operative time (mean of 200 minutes versus 287 minutes, p < 0.0001), and mean length of stay (9.5 days versus 6.6 days, p < 0.0001). Overall complication rates were similar between the groups (34.5% versus 27.5%, p = 0.177). There were no significant differences in the mean number of lymph nodes harvested (21.7 versus 22.2 nodes, p = 0.7), circumferential radial margins (1.48 cm versus 1.37 cm, p = 0.4), or in the rate of involved radial margins (10.8% versus 6.3%, p = 0.37). Five-year overall survival was 70% in the open group versus 80% in the minimally invasive group (p = 0.344), whereas the 5-year disease-free survival rate in the open group was 63.2% versus 77.6% in the minimally invasive group (p = 0.09). LIMITATIONS: This study was limited because it describes a single referral institution experience. CONCLUSIONS: Although both approaches have similar perioperative outcomes, the minimally invasive approach benefits the patients with a shorter length of stay and a lower risk for surgical wound infections. Both approaches yield similar oncological technical quality in terms of the lymph nodes harvested and margins status, and they have comparable long-term oncological outcomes. See Video Abstract at http://links.lww.com/DCR/B754.RESULTADOS A LARGO PLAZO DE LA RESECCIÓN ABDOMINOPERINEAL MÍNIMAMENTE INVASIVA VERSUS ABIERTA PARA EL CÁNCER DE RECTO: EXPERIENCIA DE UN SOLO CENTRO ESPECIALIZADOANTECEDENTES:Estudios aleatorizados han validado la proctectomía laparoscópica para el tratamiento del cáncer de recto igual a la proctectomía abierta, pero la mayoría de esos estudios han incluido resecciones con preservación del esfínter junto con resección abdominoperineal.OBJETIVO:Comparar los resultados oncológicos perioperatorios y a largo plazo entre la resección abdominoperineal abierta y mínimamente invasiva.DISEÑO:Análisis retrospectivo de una base de datos mantenida de forma prospectiva.ENTORNO CLINICO:Servicio único especializado en cirugía colorrectal.PACIENTES:Todos los pacientes que se sometieron a resección abdominoperineal por cáncer de recto primario entre 2000 y 2016.PRINCIPALES MEDIDAS DE VALORACION:Resultados oncológicos perioperatorios y a largo plazo.RESULTADOS:Se incluyeron 452 pacientes, 372 en el grupo abierto y 80 en el grupo mínimamente invasivo, con una mediana de seguimiento de 74 meses. Hubo diferencias significativas entre los grupos en términos de tratamiento con radiación neoadyuvante (67,5% del grupo abierto versus 81,3% del grupo mínimamente invasivo, p = 0,01), tiempo operatorio (media de 200 minutos versus 287 minutos, p < 0,0001) y la duración media de la estancia (9,5 días frente a 6,6 días, p < 0,0001). Las tasas generales de complicaciones fueron similares entre los grupos (34,5% versus 27,5%, p = 0,177). No hubo diferencias significativas en el número medio de ganglios linfáticos extraídos (21,7 versus 22,2 ganglios, p = 0,7), márgenes radiales circunferenciales (1,48 cm y 1,37 cm, p = 0,4), ni en la tasa de márgenes radiales afectados (10,8 cm). % versus 6,3%, p = 0,37). La supervivencia general a 5 años fue del 70% en el grupo abierto frente al 80% en el grupo mínimamente invasivo (p = 0,344), mientras que la tasa de supervivencia libre de enfermedad a 5 años en el grupo abierto fue del 63,2% frente al 77,6% en el grupo mínimamente invasivo (p = 0,09).LIMITACIONES:Experiencia en una institución de referencia única.CONCLUSIONES:Si bien ambos tienen resultados perioperatorios similares, el enfoque mínimamente invasivo, beneficia a los pacientes con estadía más corta y menor riesgo de infecciones de la herida quirúrgica. Ambos enfoques, producen una calidad técnica oncológica similar en términos de ganglios linfáticos extraídos y estado de los márgenes, y tienen resultados oncológicos comparables a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B754. (Traducción - Dr. Fidel Ruiz Healy).

Long-term sequelae of drug-induced liver injury.

Drug-induced liver injury (DILI) has a very variable clinical and biochemical phenotype and differs widely in severity, from mild injury to life-threatening liver failure. Chronic injury has also been reported to occur at a variable frequency, ranging from 3.4% to 39%, 6-12 months after discontinuing the implicated agent. This wide range is probably related to various definitions of chronic liver injury and variable selection of patients. The long-term sequalae of this chronic injury in terms of morbidity and mortality are unclear, although rare vanishing bile duct syndrome is associated with an unfavourable prognosis, with increased risk of chronic liver failure and need for liver transplantation. Other forms of long-term sequalae associated with DILI are progressive fibrosis, autoimmune-like hepatitis, secondary sclerosing cholangitis, sinusoidal obstruction syndrome and, as a common final stage, the development of cirrhosis, portal hypertension and its complications. Immune checkpoint inhibitors, which can cause an autoimmune-like phenotype have also recently been shown to cause sclerosing cholangitis with cytotoxic T CD8+ cell infiltration in biliary tracts. DILI has been shown to have a significant impact on health-related quality of life but very little is known about its psychological consequences in the long-term. Further investigations with structured long-term follow-up and periodic quality of life surveys are needed to assess the impact of DILI on psychological outcomes, particularly in those with chronic sequelae.

Community-Level Economic Distress, Race, and Risk of Adverse Outcomes After Heart Failure Hospitalization Among Medicare Beneficiaries.

BACKGROUND: Socioeconomic disadvantage is a strong determinant of adverse outcomes in patients with heart failure. However, the contribution of community-level economic distress to adverse outcomes in heart failure may differ across races and ethnicities. METHODS: Patients of self-reported Black, White, and Hispanic race and ethnicity hospitalized with heart failure between 2014 and 2019 were identified from the Medicare MedPAR Part A 100% Files. We used patient-level residential ZIP code to quantify community-level economic distress on the basis of the Distressed Community Index (quintile 5: economically distressed versus quintiles 1-4: nondistressed). The association of continuous and categorical measures (distressed versus nondistressed) of Distressed Community Index with 30-day, 6-month, and 1-year risk-adjusted mortality, readmission burden, and home time were assessed separately by race and ethnicity groups. RESULTS: The study included 1 611 586 White (13.2% economically distressed), 205 840 Black (50.6% economically distressed), and 89 199 Hispanic (27.3% economically distressed) patients. Among White patients, living in economically distressed (versus nondistressed) communities was significantly associated with a higher risk of adverse outcomes at 30-day and 1-year follow-up. Among Black and Hispanic patients, the risk of adverse outcomes associated with living in distressed versus nondistressed communities was not meaningfully different at 30 days and became more prominent by 1-year follow-up. Similarly, in the restricted cubic spline analysis, a stronger and more graded association was observed between Distressed Community Index score and risk of adverse outcomes in White patients (versus Black and Hispanic patients). Furthermore, the association between community-level economic distress and risk of adverse outcomes for Black patients differed in rural versus urban areas. Living in economically distressed communities was significantly associated with a higher risk of mortality and lower home time at 1-year follow-up in rural areas but not urban areas. CONCLUSIONS: The association between community-level economic distress and risk of adverse outcomes differs across race and ethnic groups, with a stronger association noted in White patients at short- and long-term follow-up. Among Black patients, the association of community-level economic distress with a higher risk of adverse outcomes is less evident in the short term and is more robust and significant in the long-term follow-up and rural areas.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

INTRODUCTION AND OBJECTIVES: Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. MATERIALS AND METHODS: We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. RESULTS: A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). CONCLUSIONS: HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.