Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Subgroup Analysis in Pulmonary Hypertension-Specific Therapy Clinical Trials: A Systematic Review

Pulmonary hypertension (PH) treatment decisions are driven by the results of randomized controlled trials (RCTs). Subgroup analyses are often performed to assess whether the intervention effect will change due to the patient’s characteristics, thus allowing for individualized decisions. This review aimed to evaluate the appropriateness and interpretation of subgroup analyses performed in PH-specific therapy RCTs published between 2000 and 2020. Claims of subgroup effects were evaluated with prespecified criteria. Overall, 30 RCTs were included. Subgroup analyses presented: a high number of subgroup analyses reported, lack of prespecification, and lack of interaction tests. The trial protocol was not available for most RCTs; significant differences were found in those articles that published the protocol. Authors reported 13 claims of subgroup effect, with 12 claims meeting four or fewer of Sun’s criteria. Even when most RCTs were generally at low risk of bias and were published in high-impact journals, the credibility and general quality of subgroup analyses and subgroup claims were low due to methodological flaws. Clinicians should be skeptical of claims of subgroup effects and interpret subgroup analyses with caution, as due to their poor quality, these analyses may not serve as guidance for personalized care

Correction: Smartphone Apps for Patients With Hematologic Malignancies: Systematic Review and Evaluation of Content

[This corrects the article DOI: 10.2196/35851.]

Intervención multidisciplinar para la mejora de la seguridad de los fármacos hipoglucemiantes

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Venetoclax combination therapy with hypomethylating agents in young adults with relapsed/refractory acute myeloid leukaemia

In recent years, one of the most successful advances in treating acute myeloid leukaemia (AML) has been the combination of the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax with hypomethylating agents (decitabine or azacytidine). This combination treatment has an accelerated approval by the Food and Drug Administration for newly diagnosed AML adults who are 75 years of age or older or who have comorbidities and are not eligible to receive intensive induction chemotherapy. AML is the most common form of acute leukaemia in adults, with a median age at diagnosis of 68 years. Consequently, most of the patients included in the studies are elderly. Traditionally, young patients achieve higher remission rates compared with the elderly AML population. Although venetoclax combination therapy could become a treatment option for treating young patients with relapsed/refractory AML, this regimen has not been systematically tested in this setting. In this study, we summarize the currently available evidence on the treatment of venetoclax in combination with hypomethylating agents for the treatment of young relapsed/refractory AML patients, in addition to our experience in clinical practice with two case reports. Venetoclax, combined with hypomethylating agents, seems to be an effective option for young relapsed/refractory AML patients. However, due to the poor quality of the evidence, additional well-designed studies with greater numbers of patients are needed to confirm the effectiveness and safety of venetoclax combination regimens for this population

Association between anticholinergic burden and constipation: a systematic review

The association between anticholinergic burden and constipation is not well defined and documented; for this reason, a systematic review was carried out in five databases (Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus), including studies assessing the correlation between anticholinergic burden, and constipation between January 2006 and December 2020. Data extraction was conducted independently by two researchers. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. From 2507 identified articles, 11 were selected for this review: six cross-sectional studies, four retrospective cohort studies, and a post hoc analysis of a randomized clinical trial. Overall, nine studies reported at least one statistical association between anticholinergic burden and constipation, finding 13 positive results out of 24 association measurements. A total of 211,921 patients were studied. The association between constipation and anticholinergic burden could be demonstrated in studies including 207,795 patients. Most studies were not designed to find differences in constipation prevalence and did not adjust the results by confounding factors. Our findings suggest that a correlation between anticholinergic burden and constipation exists. Higher quality-evidence studies are needed, including analysis that considers confounding factors, such as other non-pharmacological causes of constipation

Tratamiento antifúngico endovenoso domiciliario: una alternativa segura y eficaz

[EN ]Introduction: Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. Methods: Prospective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. Results: Of the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p = 0.001), IC Charlson > 2 (58.3% vs 38.8; p = 0.053), duration of treatment (15 days vs 10.39 days; p = 0.001) and patients with central catheters (54.2% vs 21.7%; p = 0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p = 0.45) or re-admissions (12.5% vs 10%; p = 0.686) and OPAT with AT was successful in 21/24 patients (87.5%). Conclusions: AT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician.[ES] Introducción: El tratamiento antimicrobiano domiciliario endovenoso (TADE) ha sido reconocido como una alternativa al tratamiento hospitalario útil, eficiente y seguro. Sin embargo, los antimicrobianos más utilizados son los antibióticos, y existe menos información sobre el uso de la terapia antimicótica (TA). El objetivo de este estudio es analizar una cohorte de pacientes tratados con TA administrada mediante TADE y compararlos con pacientes del resto de la cohorte (RC) tratados con otros antibióticos. Métodos: Estudio prospectivo observacional con análisis post hoc (o retrospectivo) de una cohorte de pacientes atendidos en el programa TADE. Seleccionamos a los pacientes tratados con antifúngicos entre julio de 2012 y diciembre de 2018. Registramos los datos demográficos y clínicos para analizar la validez del tratamiento y comparar las diferencias entre la TA y el RC. Resultados: De los 1.101 pacientes incluidos en el programa TADE, 24 (2,18%) fueron tratados con TA: 12 anfotericina B liposómica, 6 equinocandinas y 6 fluconazol. Este resultado es similar a otras cohortes. Hubo diferencias entre la TA vs. RC en el número de pacientes con neoplasia (58,3 vs. 28%; p = 0,001), índice de Charlson > 2 (58,3 vs. 38,8; p = 0,053), duración del tratamiento (15 vs. 10,39 días; p = 0,001) y pacientes con catéteres centrales (54,2 vs. 21,7%; p = 0,0001). Estas diferencias están justificadas porque en el grupo TA se incluyeron más pacientes hematológicos. Sin embargo, no hubo diferencias en las reacciones adversas (25 vs. 32,3%; p = 0,45) o reingresos (12,5 vs. 10%; p = 0,686) y el TADE con TA tuvo éxito en 21/24 pacientes (87,5%). Conclusiones: En pacientes seleccionados, clínicamente estables y en seguimiento por un médico de enfermedades infecciosas, la TA podría administrarse en programas TADE