Prostanoids for critical limb ischaemia.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010. OBJECTIVES: To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials. SELECTION CRITERIA: Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author. MAIN RESULTS: For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life. AUTHORS' CONCLUSIONS: We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.

[Cross-cultural validation and telephonic reliability of modified "VIDA" questionnaire]. / Validación transcultural y confiabilidad telefónica del cuestionario "vida diaria del anciano" modificado.

Instrumental activities scales allow the assessment of the functional status of the elderly; however, those currently used have gender bias and insufficient cross-cultural validation. The main objectives of this study were to perform the cross-cultural validation of the modified "VIDA: Daily living of the elderly questionnaire", created in Spain, into the Spanish spoken language in the City of Buenos Aires, and to evaluate its telephonic reliability. The secondary objective was to assess the concurrent validity of the modified VIDA questionnaire with the Lawton and Brody scale. The experts discussion group assessed the questionnaire vocabulary and proposed modifications according to the local language. We performed a pilot study to evaluate its comprehension, vocabulary and length. Afterwards we interviewed patients in person and after 14 days by telephone. We analyzed the global, inter and intra-observer reliability in both, the in person and the telephonic questionnaire, obtaining intra-class correlation coefficients of 0.95 (CI 95% 0.91-0.99), 0.99 (CI 95% 0.97-1.00) and 0.94 (IC 95% 0.87-1.00) respectively. Additionally, we obtained a very good correlation in both modalities between the modified VIDA questionnaire and the Lawton and Brody scale, with no differences regarding the patient's gender. In conclusion, the modified VIDA questionnaire was cross-culturally adapted in Buenos Aires City. Its implementation is reliable and valid both in person and by telephone.

Neck masses in aged patients: etiology and semiological features associated with malignancy.

INTRODUCTION: The purposes of our study were to describe the distribution of diagnoses in a series of 273 patients over 65 years of age who presented for neck masses and to identify semiological features associated with malignancy. METHODS: Neck masses were categorized as congenital lesions (n = 7, 3%, 95% CI: 1%- 5%), inflammatory masses (n = 67, 25%, 95% CI: 19%- 30%), benign neoplasms (n = 77, 28%, 95% CI: 23%- 34%), and malignant neoplasms (n = 87, 32%, 95% CI: 26%- 38%). RESULTS: A group of patients had discontinued care and, consequently, a definitive diagnosis could not be reached (n = 35, 12%). Age (OR 1.06, 95% CI 1.00-1.12), male sex (OR 2.35, 95% CI 1.11-4.96), prior history of cancer (OR 2.66, 95% CI 1.02-6.92), mass fixation to skin or deep tissues (OR 4.87, 95% CI 2.20-10.76), and the involvement of multiple cervical lymph node levels (OR 4.15, 95% CI 1.64-10.51) were identified as semiological features associated with malignancy. CONCLUSION: In the case of a neck mass in an elderly patient, its neoplastic origin should be strongly suspected.

Introducción: El objetivo de nuestro estudio fue describir la distribución de diagnósticos en una serie de 273 pacientes mayores de 65 años que consultaron por masas cervicales e identificar características semiológicas asociadas a malignidad. Métodos: Las masas cervicales fueron categorizadas como lesiones congénitas (n = 7, 3%, 95% CI: 1%- 5%), masas de origen inflamatorio (n = 67, 25%, 95% CI: 19%-30%), neoplasias benignas (n = 77, 28%, 95% CI: 23%- 34%) y neoplasias malignas (n = 87, 32%, 95% CI: 26%-38%). Resultados: Un grupo de pacientes discontinuó el tratamiento y en consecuencia no fue posible alcanzar un diagnóstico definitivo (n = 35, 12%). La edad (OR 1.06, 95% CI 1.00-1.12), el sexo masculino (OR 2.35, 95% CI 1.11-4.96), los antecedentes de cáncer (OR 2.66, 95% CI 1.02-6.92), la fijación de la masa a los planos profundos o a piel (OR 4.87, 95% CI 2.20-10.76) y la afectación de más de un nivel ganglionar del cuello (OR 4.15, 95% CI 1.64-10.51) fueron identificados como características semiológicas asociadas a malignidad. Conclusión: En presencia de una masa cervical en un paciente adulto mayor debe existir una fuerte sospecha de origen neoplásico.

Pregnancy outcomes of women with multiple sclerosis treated with ocrelizumab in Canada: A descriptive analysis of real-world data.

OBJECTIVES: To report and describe the real-world use of ocrelizumab in women with multiple sclerosis (MS) in Canada before and/or during pregnancy as well as their fetal outcomes. METHODS: We identified retrospective and prospective Canadian pregnancy exposure cases from the Roche Global Safety Database from November 5, 2008 until March 31, 2021, and linked these cases to information within the Canadian Roche Patient Support Program (COMPASS). The analysis only included spontaneous reports or those from a non-interventional program. Details of the pregnancy exposures, fetal outcomes, as well as relevant patient characteristics, were collected. RESULTS: A total of 107 cases of maternal exposures were retrieved, with 104 (97.2%) being prescribed ocrelizumab for relapsing-remitting MS (RRMS) and 105 (98.1%) being reported from the COMPASS program. Of these cases, 85 (79.4%) were prospective and 22 (20.6%) retrospective. Cases were pooled (n = 65), and unknown/lost to follow-up outcomes and ongoing pregnancies were excluded. All cases reporting an outcome were analyzed, including 47 (72.3%) live births (44.7% full term, 8.5% preterm, 46.8% unknown gestational age), 13 (20.0%) spontaneous abortions, 2 (3.1%) therapeutic abortions/elective terminations, and 3 (4.6%) ectopic pregnancies. One major congenital anomaly of the limb (polydactyly) was reported; however, multiple confounders were likely contributors. Of the total maternal exposures (n = 107), 50 cases (46.6%) were not exposed to ocrelizumab in utero, with 32 of these (64.0%) receiving their last ocrelizumab infusion >3 but ≤6 months prior to conception, 17 (34.0%) receiving it >6 months prior to conception and 1 case receiving it at an unknown time point not in utero. Among the 37 (34.6%) maternal exposure cases exposed in utero, 22 (59.5%) received their last ocrelizumab infusion ≤3 months prior to conception. CONCLUSION: The data presented, although not without limitations, continues to suggest no increased risk of congenital anomalies and are consistent with ocrelizumab global pregnancy safety data and epidemiological rates.

A multicentre real-world data study to assess the bleeding rate and management of patients with haemophilia A and factor VIII inhibitors in Argentina.

The development of inhibitors against factor VIII (FVIII) concentrates is a severe complication of treatment for patients with haemophilia. We investigated annualized bleeding rates (ABRs) in patients in Argentina with haemophilia A with inhibitors and analysed potential differences between treatment strategies. This multicentre, retrospective, real-world data, cohort design study comprised ambulatory paediatric and adult patients with congenital haemophilia A and FVIII inhibitors treated according to standard clinical practice, with 12-months follow-up. Of 69 included patients, 39 (56.5%) received on-demand treatment, 13 (18.8%) received prophylactic treatment, and 17 (24.6%) received immune tolerance induction (ITI) therapy. The mean overall ABR was 7.68 ±â€Š8.18, with similar rates for on-demand (8.59 ±â€Š9.69), prophylaxis (5.54 ±â€Š4.71), and ITI (7.24 ±â€Š6.23) subgroups. In the negative binomial regression model, prophylactic treatment [incidence rate ratio (IRR) 0.41, 95% confidence interval (CI): 0.21-0.79, P < 0.01] and ITI (IRR 0.47, 95% CI: 0.27-0.81, P < 0.01) therapy were significantly associated with a decrease in the ABR compared with on-demand treatment. Age (IRR 0.96, 95% CI: 0.94-0.97, P < 0.01), number of target joints (IRR 1.21, 95% CI: 1.11-1.31, P < 0.001), and history of recurring bleeding (IRR 2.3, 95% CI: 1.19-4.57, P = 0.012) were significantly and independently associated with ABR. The ABR in standard clinical practice was lower than that reported in controlled clinical trials. Patients undergoing prophylaxis and ITI therapy showed reduced ABRs compared with on-demand treatment, after controlling for bleeding predictor variables.

Baseline Functional Status and One-year Mortality After Hospital Admission in Elderly Patients: a prospective cohort study.

INTRODUCTION: Hospitalization represents a major factor that may precipitate the loss of functional status and the cascade into dependence. The main objective of our study was to determine the effect of functional status measured before hospital admission on survival at one year after hospitalization in elderly patients. METHODS: Prospective cohort study of adult patients (over 65 years of age) admitted to either the general ward or intensive Care units (ICU) of a tertiary teaching hospital in Buenos Aires, Argentina. Main exposure was the pre-admission functional status determined by means of the modified "VIDA" questionnaire, which evaluates the instrumental activities of daily living. We used a multivariate Cox proportional hazards model to estimate the effect of prior functional status on time to all-cause death while controlling for measured confounding. Secondarily, we analyzed the effect of post-discharge functional decline on long-term outcomes. RESULTS: 297 patients were included in the present study. 12.8% died during hospitalization and 86 patients (33.2%) died within one year after hospital discharge. Functional status prior to hospital admission, measured by the VIDA questionnaire (e.g., one point increase), was associated with a lower hazard of all-cause mortality during follow-up (Hazard Ratio [HR]: 0.96; 95% Confidence Interval [CI]: 0.94-0.98). Finally, functional decline measured at 15 days after hospital discharge, was associated with higher risk of all-cause death during follow-up (HR: 2.19, 95% CI: 1.09-4.37) Conclusion: Pre-morbid functional status impacts long term outcomes after unplanned hospitalizations in elderly adults. Future studies should confirm these findings and evaluate the potential impact on clinical decision-making.

Introducción: La hospitalización representa un factor que puede favorecer la pérdida de la funcionalidad. El objetivo principal de este estudio fue determinar el efecto de la funcionalidad previa a la admisión hospitalaria sobre la sobrevida al año del egreso, en pacientes adultos mayores. Métodos: Este estudio de cohorte prospectiva incluyó pacientes de 65 años o mayores que fueron hospitalizados en la sala general o la unidad de terapia intensiva en un hospital universitario de la ciudad de Buenos Aires, Argentina. La funcionalidad basal fue medida a través del cuestionario VIDA modificado, el cual evalúa las actividades instrumentales de la vida diaria. Utilizamos un modelo multivariable de Cox para estimar el efecto de la funcionalidad basal sobre la sobrevida al año posterior al egreso, el cual permitió ajustar por potenciales confundidores. Además, analizamos el efecto de la funcionalidad luego del egreso hospitalario sobre la mortalidad al año del mismo. Resultados: Se incluyeron 297 pacientes, de los cuales 12.8% fallecieron durante la hospitalización, y 86 pacientes (33.2%) fallecieron dentro del año del egreso hospitalario. Un aumento de un punto en la escala de la funcionalidad basal (es decir, mejor funcionalidad), se asoció a una disminución en el riesgo de muerte al año del egreso (Hazard Ratio [HR]: 0.96; Intervalo de confianza [IC] 95%: 0.94­0.98). Por ultimo, la declinación funcional posterior al egreso hospitalario se asoció a un mayor riesgo de muerte durante el seguimiento (HR: 2.19, IC 95%: 1.09­4.37). Conclusión: La funcionalidad previa a la hospitalización de los adultos mayores impacta en los resultados a largo plazo luego de una hospitalización.

Neck masses in aged patients: etiology and semiological features associated with malignancy / Masas cervicales en adultos mayores: Etiología y características semiológicas asociadas a malignidad

Abstract Introduction: The purposes of our study were to describe the distribution of diagnoses in a series of 273 patients over 65 years of age who presented for neck masses and to identify semiological fea tures associated with malignancy. Methods: Neck masses were categorized as congenital lesions (n = 7, 3%, 95% CI: 1%- 5%), inflammatory masses (n = 67, 25%, 95% CI: 19%- 30%), benign neoplasms (n = 77, 28%, 95% CI: 23%- 34%), and malignant neoplasms (n = 87, 32%, 95% CI: 26%- 38%). Results: A group of patients had discontinued care and, consequently, a definitive diagnosis could not be reached (n = 35, 12%). Age (OR 1.06, 95% CI 1.00-1.12), male sex (OR 2.35, 95% CI 1.11-4.96), prior history of cancer (OR 2.66, 95% CI 1.02-6.92), mass fixation to skin or deep tissues (OR 4.87, 95% CI 2.20-10.76), and the involvement of multiple cervical lymph node levels (OR 4.15, 95% CI 1.64-10.51) were identified as semiological features associated with malignancy. Conclusion: In the case of a neck mass in an elderly patient, its neoplastic origin should be strongly suspected.

Resumen Introducción: El objetivo de nuestro estudio fue describir la distribución de diagnósticos en una serie de 273 pacientes mayores de 65 años que consultaron por masas cervicales e identificar características semiológicas asociadas a malignidad. Métodos: Las masas cervicales fueron categorizadas como lesiones congénitas (n = 7, 3%, 95% CI: 1%- 5%), masas de origen inflamatorio (n = 67, 25%, 95% CI: 19%-30%), neoplasias benignas (n = 77, 28%, 95% CI: 23%- 34%) y neoplasias malignas (n = 87, 32%, 95% CI: 26%-38%). Resultados: Un grupo de pacientes discontinuó el tratamiento y en consecuencia no fue posible alcanzar un diagnóstico defini tivo (n = 35, 12%). La edad (OR 1.06, 95% CI 1.00-1.12), el sexo masculino (OR 2.35, 95% CI 1.11-4.96), los antecedentes de cáncer (OR 2.66, 95% CI 1.02-6.92), la fijación de la masa a los planos profundos o a piel (OR 4.87, 95% CI 2.20-10.76) y la afectación de más de un nivel ganglionar del cuello (OR 4.15, 95% CI 1.64-10.51) fueron identificados como características semiológicas asociadas a malignidad. Conclusión: En presencia de una masa cervical en un paciente adulto mayor debe existir una fuerte sospecha de origen neoplásico.

Validación transcultural y confiabilidad telefónica del cuestionario "vida diaria del anciano" modificado / Cross-cultural validation and telephonic reliability of modified "VIDA" questionnaire

Las escalas que evalúan las actividades instrumentales de la vida diaria permiten la valoración del estado funcional de los ancianos; sin embargo, las utilizadas habitualmente presentan sesgo de género e insuficiente validación transcultural. El objetivo principal de este estudio fue efectuar la validación transcultural del “Cuestionario VIDA: Vida Diaria del anciano” modificado, creado en España, al castellano de habla usual en la Ciudad de Buenos Aires y la evaluación de su confiabilidad en forma telefónica. Como objetivo secundario, evaluamos su validez concurrente con respecto a la escala de Lawton y Brody, tanto en forma presencial como telefónica. El grupo de discusión de expertos evaluó el vocabulario original del cuestionario y propuso modificaciones de acuerdo a la cultura local. Realizamos una prueba piloto para valorar el vocabulario, su comprensión y su longitud. Posteriormente encuestamos pacientes de manera presencial y a los 14 días de manera telefónica. Analizamos la confiabilidad global, inter e intraobservador, del cuestionario presencial y re-test telefónico, obteniéndose coeficientes de correlación intraclase de 0.95 (IC 95% 0.91 - 0.99), 0.99 (IC 95% 0.97-1.00) y 0.94 (IC 95% 0.87-1.00) respectivamente. Adicionalmente, obtuvimos muy buena correlación en ambas modalidades entre el cuestionario VIDA modificado y la escala de Lawton y Brody, sin diferencias en cuanto al género de los pacientes. En conclusión, el cuestionario VIDA modificado fue adaptado transculturalmente en la Ciudad de Buenos Aires. Su implementación es confiable y válida tanto de manera presencial como telefónica.

Instrumental activities scales allow the assessment of the functional status of the elderly; however, those currently used have gender bias and insufficient cross-cultural validation. The main objectives of this study were to perform the cross-cultural validation of the modified “VIDA: Daily living of the elderly questionnaire”, created in Spain, into the Spanish spoken language in the City of Buenos Aires, and to evaluate its telephonic reliability. The secondary objective was to assess the concurrent validity of the modified VIDA questionnaire with the Lawton and Brody scale. The experts discussion group assessed the questionnaire vocabulary and proposed modifications according to the local language. We performed a pilot study to evaluate its comprehension, vocabulary and length. Afterwards we interviewed patients in person and after 14 days by telephone. We analyzed the global, inter and intra-observer reliability in both, the in person and the telephonic questionnaire, obtaining intra-class correlation coefficients of 0.95 (CI 95% 0.91-0.99), 0.99 (CI 95% 0.97-1.00) and 0.94 (IC 95% 0.87-1.00) respectively. Additionally, we obtained a very good correlation in both modalities between the modified VIDA questionnaire and the Lawton and Brody scale, with no differences regarding the patient´s gender. In conclusion, the modified VIDA questionnaire was cross-culturally adapted in Buenos Aires City. Its implementation is reliable and valid both in person and by telephone.

Agranulocitosis por clozapina: un paradigma de la relación costo-beneficio / Clozapine-induced agranulocytosis: A Paradigm of the cost-benefit relationship

La clozapina es una herramienta terapéutica altamente eficaz utilizada en el tratamiento sintomático de la esquizofrenia. A pesar de los beneficios que brinda en dichos pacientes, su uso se ha restringido debido a la aparición potencialmente letal de agranulocitosis, un efecto adverso idiosincrático, cuya fisiopatología permanece aún desconocida. A través de esta revisión bibliográfica, se analizarán los principales aspectos clínicos de este efecto adverso, se expondrán las actuales indicaciones del fármaco y se evaluará el costo-beneficio de su indicación.

Clozapine is a highly effective therapeutic tool that is used for the treatment of schizophrenia symptoms. Despite its benefits on patients with such disease, its use has been restricted due to the potentially lethal appearance of agranulocytosis, an idiosyncratic adverse effect whose pathology still remains unknown. In this review, the author will analyze the main clinical aspects of this adverse effect, describe the current prescriptions of this pharmacological drug and evaluate the cost-benefit of its prescription.