Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer.
In this ...double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase.
In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval CI, 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache.
The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)
People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, ...there is scant evidence to support a standard treatment duration.
To test differing durations of intravenous antimicrobials for CF exacerbations.
STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7-10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days' total antimicrobial duration; all others were randomized to 14 or 21 days' duration.
The primary outcome was percent predicted FEV
(ppFEV
) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV
change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI ‒3.3 to 2.0), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV
changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive.
Among adults with CF with early treatment improvement during exacerbation, ppFEV
after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).
•The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) global pandemic has significantly impacted CF clinical research.•An electronic survey was sent to Therapeutic Development Network (TDN) ...sites to monitor the impact.•SARS-CoV-2 had an early impact on participant enrollment, research team stability, and procedures such as spirometry and sputum induction.•Trends steadily improved over the months as research activities began to recover across the TDN.•SARS-CoV-2 highlights new opportunities to expand CF research focusing on data collection outside of research centers and increased access for remote participation.
The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) global pandemic significantly impacted CF clinical research within the Cystic Fibrosis Foundation Therapeutics Development Network (CFF TDN). A Research Electronic Data Capture (REDCap) survey was developed and sent to network sites to monitor and understand the impact on research teams, ongoing and anticipated clinical research, and specific clinical and research procedures. Key findings indicated an early impact on participant enrollment, research team stability, and procedures such as spirometry and sputum induction. These trends steadily improved over the months as research activities began to recover across the TDN. While SARS-CoV-2 created a significant challenge it also highlights new opportunities to expand CF research with greater focus on data collection outside of research centers and increased access for remote participation.
Most individuals with mood disorders experience psychiatric and/or medical comorbidity. Available treatment guidelines for major depressive disorder (MDD) and bipolar disorder (BD) have focused on ...treating mood disorders in the absence of comorbidity. Treating comorbid conditions in patients with mood disorders requires sufficient decision support to inform appropriate treatment.
The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force sought to prepare evidence- and consensus-based recommendations on treating comorbid conditions in patients with MDD and BD by conducting a systematic and qualitative review of extant data. The relative paucity of studies in this area often required a consensus-based approach to selecting and sequencing treatments.
Several principles emerge when managing comorbidity. They include, but are not limited to: establishing the diagnosis, risk assessment, establishing the appropriate setting for treatment, chronic disease management, concurrent or sequential treatment, and measurement-based care.
Efficacy, effectiveness, and comparative effectiveness research should emphasize treatment and management of conditions comorbid with mood disorders. Clinicians are encouraged to screen and systematically monitor for comorbid conditions in all individuals with mood disorders. The common comorbidity in mood disorders raises fundamental questions about overlapping and discrete pathoetiology.
Handoffs of patient care are a leading root cause of medical errors. Standardized techniques exist to minimize miscommunications during verbal handoffs, but studies to guide standardization of ...printed handoff documents are lacking.
To determine whether variability exists in the content of printed handoff documents and to identify key data elements that should be uniformly included in these documents.
Pediatric hospitalist services at 9 institutions in the United States and Canada.
Sample handoff documents from each institution were reviewed, and structured group interviews were conducted to understand each institution's priorities for written handoffs. An expert panel reviewed all handoff documents and structured group-interview findings, and subsequently made consensus-based recommendations for data elements that were either essential or recommended, including best overall printed handoff practices.
Nine sites completed structured group interviews and submitted data. We identified substantial variation in both the structure and content of printed handoff documents. Only 4 of 23 possible data elements (17%) were uniformly present in all sites' handoff documents. The expert panel recommended the following as essential for all printed handoffs: assessment of illness severity, patient summary, action items, situation awareness and contingency plans, allergies, medications, age, weight, date of admission, and patient and hospital service identifiers. Code status and several other elements were also recommended.
Wide variation exists in the content of printed handoff documents. Standardizing printed handoff documents has the potential to decrease omissions of key data during patient care transitions, which may decrease the risk of downstream medical errors.
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