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Background The CARD study demonstrated superiority of cabazitaxel over abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel and progressed ≤12 months on the alternative androgen-receptor-targeted agent (ARTA). The objective was to compare characteristics and treatment patterns of patients from a real-world dataset with the CARD population. Methods Real-world data were collected from Medimix Live TrackerTM, a retrospective, global oncology database of healthcare professional-reported electronic patient medical forms (2001–2019), with data from patients from Europe, USA, Brazil and Japan. The database contained patient, tumor and treatment information for 12,140 patients who received ≥1 line of treatment for mCRPC. A CARD-like cohort included patients treated with docetaxel, prior abiraterone/enzalutamide and cabazitaxel. Results A large proportion of patients received ≥2 lines of ARTA (35.1%) with 42% of patients who received a first-line ARTA receiving another ARTA in second line. Of the total patients, 452 were eligible for the CARD-like cohort. Median age of the CARD-like cohort was comparable to CARD (73 vs 70 years). The CARD-like cohort had unfavorable disease characteristics vs CARD: ECOG PS ≥ 2 (45% vs 4.7%); metastasis at diagnosis (46% vs 38%) and Gleason 8–10 (65% vs 57%). More patients in the CARD-like cohort received ARTA before docetaxel (48% vs 39%) and received the first ARTA for >12 months (30% vs 17%) compared with CARD. Despite more patients in the CARD-like cohort receiving the lower 20 mg/m2 dose of cabazitaxel (55% vs 21%), cabazitaxel treatment duration was similar (21.9 vs 22.0 weeks). Conclusions Sequential use of ARTA was frequent. Results indicate the CARD population is reflective of routine clinical practice and duration of response to cabazitaxel was similar in a real-world population.

Background Morbidity and Mortality (M&M) conferences allow clinicians to review adverse events and identify areas for improvement. There are few reports of structured M&M conferences in low- and middle-income countries and no report of collaborative efforts to standardize them. Methods The present study aims to gather general surgeons representing most of Peru’s urban surgical care and, in collaboration, with trauma quality improvement experts develop a M&M conferences toolkit with the expectation that its diffusion impacts their reported clinical practice. Fourteen general surgeons developed a toolkit as part of a working group under the auspices of the Peruvian General Surgery Society. After three years, we conducted an anonymous written questionnaire to follow-up previous observations of quality improvement practices. Results A four-component toolkit was developed: Toolkit component #1: Conference logistics and case selection; Toolkit component #2: Documenting form; Toolkit component #3: Presentation template; and Toolkit component #4: Code of conduct. The toolkit was disseminated to 10 hospitals in 2016. Its effectiveness was evaluated by comparing the results of surveys on quality improvement practices conducted in 2016, before toolkit dissemination (101 respondents) and 2019 (105 respondents). Lower attendance was reported by surgeons in 2019. However, in 2019, participants more frequently described “improve the system” as the perceived objective of M&M conferences (70.5% vs. 38.6% in 2016; p Conclusion We established a toolkit for the national dissemination of a standardized M&M conference. Three years following the initial assessment in Peru, we found similar practice patterns except for increased reporting of “system improvement” as the goal of M&M conferences.

Macrophages are ubiquitously distributed throughout the various tissues of the body and perform many functions including the orchestration of inflammatory responses against pathogens by classically activated M1 macrophages and the regulation of wound healing and tissue remodeling by anti-inflammatory, alternatively activated M2 macrophages. The responsibility for these pleiotropic functions lies in the expression of a myriad of surface receptors unique to given subsets of macrophages. Much of what we know about the function of human macrophage subsets has been gleaned by studying in vitro generated macrophages matured in the presence of GM-CSF or M-CSF and polarized with different cytokines. Oftentimes, culture conditions, such as the type of serum used, the duration of the culture, and the use of polarizing cytokines, vary between studies making direct comparisons difficult. Sample preparation and processing (e.g., Ficoll

Family members of critically ill patients with COVID-19 have described increased symptoms of Post-Traumatic Stress Disorder (PTSD). Little is known about how these symptoms may change over time.We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12-months.This prospective, multi-site observational cohort study recruited participants at 12 hospitals in 5 states. Calls were made to participants at 3-4 months, 6-months, and 12-months post-patient admission to the ICU.There were 955 eligible family members, of whom 330 (53.3% of those reached) consented to participate. Complete longitudinal data was acquired for 115 individuals (34.8% of consented). PTSD symptoms were measured by the Impact of Events Scale-6 (IES-6), with a score of ≥10 identifying significant symptoms. At 3-months, the mean IES-6 score was 11.9±6.1 with 63.6% having significant symptoms, decreasing to 32.9% at one year (mean IES-6 score 7.6±5.0). Three clusters of symptom evolution emerged over time: persistent symptoms (34.8%, n=40), recovered symptoms (33.0%, n=38) and non-development of symptoms (32.2%, n=37). While participants identifying as Hispanic demonstrated initially higher adjusted IES-6 scores (2.57 points higher [95% CI: 1.1, 4.1, p =0.001]), they also demonstrated a more dramatic improvement in adjusted scores over time (4.7 greater decrease at 12 months [95% CI: 3.2-6.3, p.001]).One year later, some family members of patients with COVID-19 continue to experience significant symptoms of PTSD. Further studies are needed to better understand how various differences contribute to increased risk for these symptoms.

"Smart"-scales are a new tool for frequent monitoring of weight change as well as weigh-in behavior. These scales give researchers the opportunity to discover patterns in the frequency that individuals weigh themselves over time, and how these patterns are associated with overall weight loss. Our motivating data come from an 18-month behavioral weight loss study of 55 adults classified as overweight or obese who were instructed to weigh themselves daily. Adherence to daily weigh-in routines produces a binary times series for each subject, indicating whether a participant weighed in on a given day. To characterize weigh-in by time-invariant patterns rather than overall adherence, we propose using hierarchical clustering with dynamic time warping (DTW). We perform an extensive simulation study to evaluate the performance of DTW compared to Euclidean and Jaccard distances to recover underlying patterns in adherence time series. In addition, we compare cluster performance using cluster validation indices (CVIs) under the single, average, complete, and Ward linkages and evaluate how internal and external CVIs compare for clustering binary time series. We apply conclusions from the simulation to cluster our real data and summarize observed weigh-in patterns. Our analysis finds that the adherence trajectory pattern is significantly associated with weight loss.

IMPORTANCE: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. OBJECTIVE: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. EXPOSURE: Having a family member in the ICU with COVID-19. MAIN OUTCOMES AND MEASURES: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). RESULTS: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients’ child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P

Forty-four million US licensed drivers are ≥65 years old and at higher crash risk. Decision-making about stopping or continuing driving is difficult and often involves family and friends. This study examines if decision conflict about changing driving habits is associated between older adult drivers and their study partners (SPs) (i.e., family member or friend). Data were from a multi-site trial assessing a driving decision aid. Decision conflict about stopping or continuing driving for drivers and their SPs were measured with the Decision Conflict Scale (DCS). Dyadic associations between drivers’ and SPs’ DCS scores pre- and post-decision aid implementation were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, driver mean (SD) age was 77.1 (5.1) years; 50.0% female; 98.7% non-Hispanic; 94.7% white; and 97.8% urban-dwelling. SPs mean age was 66.1 years (13.9); 65.8% female; 95.6% non-Hispanic; 92.1% white; and commonly the driver’s spouse (54.6%) or adult child (21.1%). Most drivers (71.7%) and SPs (63.3%) had baseline DCS scores < 25 (drivers mean 18.5 (SD 12.3); SPs 20.5 (16.8)), suggesting low decision conflict. DCS was correlated within dyads at baseline (r=0.18, p < 0.01), and baseline DCS was associated with post-decision aid DCS (p < 0.001 for SPs [β=0.73] and drivers [β=0.73]). While SPs’ baseline DCS was not associated with drivers’ post-decision aid DCS, drivers’ baseline DCS and SPs’ post-decision DCS were (β=0.10; p=0.036). Higher decision conflict about driving felt by older drivers is frequently shared by their SPs, in whom decision conflict may persist even after a driving decision aid intervention.

The decision to stop or continue driving can be challenging for older adults. In a prospective two-arm randomized trial, we sought to test whether an online driving decision aid (DDA) would improve decision quality. We recruited 301 English-speaking licensed drivers, age ≥70 years, without significant cognitive impairment but with ≥1 diagnosis associated with increased likelihood of driving cessation, from clinics associated with study sites in three states. They were randomized to view 1) the online Healthwise® DDA for older adults addressing “Is it time to stop driving?”; or 2) a control condition of web-based information. Our primary outcome was decision conflict as estimated by the Decisional Conflict Scale (DCS; lower scores indicate higher quality). Secondary outcomes were knowledge and decision self-efficacy about driving decisions. We examined differences in post-randomization outcomes by study arm using generalized linear mixed-effects models with adjustment for site and pre-randomization scores. Intervention participants had a lower mean DCS score (12.3 DDA vs 15.2 control; p=0.017) and a higher mean knowledge score (88.9 DDA vs 79.9 control; p=0.038); we found no difference between groups in self-efficacy scores. The DDA had high acceptability; 86.9% of those who viewed it said they would recommend it to others in similar situations.The online Healthwise® DDA decreased decision conflict and increased knowledge in this sample of English-speaking, older adults without significant cognitive impairment. Use of such resources in clinical or community settings may support older adults as they transition from driving to other forms of mobility.

Stimulated Raman scattering is ubiquitous in many high-intensity laser environments. Parametric four-wave mixing between the pump and Raman sidebands can affect the Raman gain, but stringent phase matching requirements and strongly nonlinear dynamics obscure clear understanding of its effects at high laser powers. Here we investigate four-wave mixing in the presence of strong self-focusing and weak ionization at laser powers above the Kerr critical power. Theoretical analysis shows that the plasma generated at focus naturally leads to phase matching conditions suitable for enhanced Raman gain, almost without regard to the initial phase mismatch. Multidimensional nonlinear optical simulations with multiphoton and collisional ionization confirm the enhancement and suggest that it may lead to significantly higher Raman losses in some high-intensity laser environments.

To report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities.We conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS.PRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS.PRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.