Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

American Splendor (2003) De Shari Springer Berman y Robert Pulcini: Un superhéroe undergound con cáncer / American Splendor (2003) by Shari Springer Berman and Robert Pulcini: An Underground Superhero with Cancer

Durante la década de los 60, la auténtica cuna del cómic underground estaba en los Estados Unidos. Estas publicaciones surgieron al margen de las grandes potencias de la edición, impresión y distribución de la época, concentrándose en los temas preferidos por la contracultura: política, jazz, música rock, uso recreativo de las drogas y sexo. Se desarrollaron al margen de las tiras cómicas de los diarios más populares, los cuadernos, las revistas y los comic books que presentaban las caricaturas y las aventuras de personajes románticos, bélicos y policiacos. Pero también las de los superhéroes fantásticos favoritos del público, como Superman, materializadas por primera vez en 1938 gracias a la maestría de Joe Shuster y Jerry Siegel. En San Francisco, a comienzos de 1968, Zap Comix editó el primer comic book underground completo del dibujante Robert Crumb, emblemático pionero de estas publicaciones. Precisamente en el otoño de 1962, un mercadillo de discos de jazz de segunda mano en Cleveland propició el primer encuentro entre Robert Crumb, a la sazón un modesto dibujante de postales, y Harvey Pekar, un anodino individuo desaliñado y fracasado, que acabaría trabajando hasta su jubilación como archivero en un hospital de veteranos del gobierno federal. Así se gestó American Splendor, la autobiografía de Harvey Pekar, poética catarsis personal que sería ilustrada por algunos de los autores más representativos del cómic underground, como el propio Robert Crumb, Gary Dumm, Joe Sacco, Frank Stack y Joe Zabel. En 1987, la primera recopilación de American Splendor ganó el American Book Award. En 1994, la novela gráfica Our Cancer Year, la experiencia del cáncer padecida por Harvey Pekar en primera persona, fue escrita en colaboración con su esposa Joyce Brabner, siendo galardonada con el prestigioso premio Harvey de la industria estadounidense del cómic. (AU)

During the 1960s of the 20th century, The United States become the genuine cradle of underground comics. These publications emerged outside of the large publishing, printing and distribution industries on the day, concentrating on the major topics of the counterculture, such as politics, rock and jazz music, recreational drug use and sex. They developed outside the comic strips of the most popular daily characters, notebooks, magazines and comic books that presented the adventures of cartoons and romantics, war and police, as well as those of the most popular fantastic superheroes, such Superman, created in 1938 by Joe Shuster and Jerry Siegel. In San Francisco, at the beginning of 1968, Zap Comix published the first complete underground comic book by cartoonist Robert Crumb, the emblematic pioneer of this type of publications. Precisely, in the fall of 1962, a second-hand jazz record market in Cleveland led to the meeting between Robert Crumb, then a modest postcard artist, and Harvey Pekar, a bland individual, unkempt and unsuccessful who would end up working until his retirement as a file clerk in a federal government veterans hospital. This is how American Splendor was conceived, Harvey Pekar´s autobiography written as a poetic personal catharsis, and which would be illustrated by representative authors of underground comics such as Robert Crumb himself, Gary Dumb, Joe Sacco, Frank Stack and Joe Zabel. In 1987, the first collection of American Splendor won the American Book Award. In 1994, the graphic novel Our Cancer Year, the particular cancerous experience suffered by Harvey Pekar, written in collaborations with his wife Joyce Brabner, was awarded the prestigious Harvey Award of the American comics industry. (AU)

Ampollas, úlceras y costras en paciente con infección VIH / Blisters, scars and healing crusts in a HIV infected patient

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